Overview

1. CRRT PrescriptionAkash DeepDirector - PICU King’s College HospitalLondonChairRenal/CRRT SectionEuropean Society of Pediatric and Neonatal Intensive Care (ESPNIC) 0

2. Overview Vascath – Size , location Rates & Dose Blood flow Dialysis fluid Replacement fluid Ultrafiltration rate Anticoagulation Drug Dose Suggested Not necessarily a recipe

3. Is there a “typical” prescription? • CRRT for AKI or Sepsis or Liver failure • does the dose matter ? • Modality : Do you do convective or diffusive or both , does it matter? • Blood Flow rate: based upon the size of the child or what the vascular access can give you? • Anticoagulation – Which, when, dose, mode of delivery • Drug dosing – a perennial debate!!!!

4. Essential steps in CRRT Prescription • Decide the Indication to start CRRT • PRESCRIBE: • VASCULAR ACCESS – Size Location • Haemofilter and appropriate Sized Blood line set • Priming Solution • Blood Flow • Modality /Dose – Replacement Fluid/Dialysis Fluid • Prescribe Fluid loss rate • Prescription of electrolyte corrections • Anticoagulation – Dose,Modality, Monitoring • Drug Dosing

5. Blood flow rate • Qb • Age & weight – based • Promote circuit lifespan + patient stability: clots vs alarms • Highly access-dependent • Aim return access pressures ~ < 200 mmHg, no alarms • Start lower and increase by about 10 minutes (?) – 50% of target • and then go up 10% every 10 minutes till desired flow reached

6. Blood flow rate • No set “perfect rates” • From 3 to ~10 ml/kg/min, depending on age though • we use minimum of 50 mls/min for newborns • Examples: • 0-10 kg: 25-50ml/min • 11-20kg: 80-100ml/min • 21-50kg: 100-150ml/min • >50kg: 150-180ml/min • Neonates 8 to 12 ml/kg/min • Children 4 to 8 ml/kg/min • Older 2 to 4 ml/kg/min. • Most not > 200 ml/min: not dangerous just not necessary Based on previously most commonly used machine

7. Blood flow rate • May need to modify: • - Patient hemodynamics – initial and subsequent • which might change with CRRT • - Be aware of access and return pressure • - Visually inspect filter for clots • - Trans-membrane pressure – may need to increase blood flow

8. Treatment Dose

9. Dialysis and Replacement Fluid Rates: Clearance & Dose • Clearance mostly a function of: • Dialysis fluid flow rate (Qd) • Replacement fluid flow rate (Qr) • Molecular weight and sieving coefficient • Higher rates • = higher clearance for IEM, drug removal, severe high K • = more middle molecule clearance (CVVH/CVVHDF) • = more hypophosphatemia, kalaemia, magnesaemia • = more amino acid losses • = more drug clearance • = more work to change bags, give electrolyte infusions Qd + Qr (CVVHDF)

10. Dialysis and Replacement Fluid Rates: Clearance & Dose Urea clearance ~ 30-40 ml/min/1.73msq • No well-defined right “dose” of clearance. • For CRRT: mostly expressed in terms of effluent(ml/kg) per hour “Standard” suggestion: Qd or Qr or Qd+Qr ~ 40-60 ml/kg/hour OR 2 to 2.5 liters/hr/1.73msq. Some do much higher: some machines as high as 8L/hour REALIZE: What you prescribe is not necessarily what the patient gets!! Time off circuit, microclots in filter over time, predilution

11. Prescribed and Delivered therapy dose • Typically, therapy dose would be prescribed at 35 ml/kg/hr, in practice the delivered therapy dose was on average 8ml/kg/hr less. • Prescription should exceed that calculated to be adequate because of the known gap. • Why might we ‘lose’ significant amounts of therapy dose? • Recirculation in vascular access • High filtration fractions • Filter clogging and clotting • Troubleshooting skills • Changing of circuits • Filter down time Vesconi et al Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury Crit care 2009 13 (2);r57

12. CVVH Qr = 300 ml/hour 10 kg child: 30 ml/kg/hr “clearance”OR ~ 0.26 msq: 2L/1.73msq/hour = 300 ml/hour CVVHDF Qd = 150ml/hour Qr = 150 ml/hour CVVHD Qd = 300 ml/hour

13. 425 patients Endpoint = survival 15 days after D/C HF 146 UF rate 20ml/kg/hr survival significantly lower in this group compared to the others 139 UF rate 35ml/kg/hr p=0.0007 140 UF rate 45ml/kg/hr p=0.0013 Dialysis Dose and OutcomeRonco et al. Lancet 2000; 351: 26-30 Conclusions: • Minimum UF rates should be ~ 35 ml/kg/hr • Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration

15. ATN Study

17. Randomised Evaluation of Normal vs Augmented Level Replacement (RENAL) Therapy ) • 1500 critically ill adults • CVVHDF • 25 ml/kg/hour • 40 ml/kg/hour Mortality at 28 days was similar in the higher-intensity and lower-intensity treatment groups (38.5% and 36.9%, respectively), and mortality at 90 days was the same (44.7%) in both groups.

18. Does the dose of solution exposure per unit of time matter • These adult studies have failed to note a dose response curve of survival • These studies are flawed for IHD vs CRRT was compared and CRRT was both convective and diffusive

19. So • If you start with a standard prescription • Eg • BFR 5-10 mls/kg/min (access dependent) • Membrane surface area proportional to patient body surface area • Decision of convective or diffusive at approx 2000-3000/mls/hr/1.73m2

20. and • If the marker of your clearance is not achieved • E.g. • inadequate clearance of Urea, Ammonia, intoxicant, lactate • Then increase your solution exposure per unit of time • Maximize convective clearance before adding diffusive clearance • Consider increasing the BFR and increasing surface area of the membrane • Filter downtimes to be minimised

21. Solutions • CVVHD – dialysis fluid for diffusive clearance • CVVH – replacement fluid: • replacing fluid you are removing to achieve solute • clearance by convection • CVVHDF – both • Priming solutions – Saline /blood prime • Anticoagulant solutions • Using these to correct metabolic abnormalities (remove) and • prevent treatment-related metabolic abnormalities (replace).

22. Dialysis fluid? Replacement fluid? • Personal suggestion: use the same solution • If needed (e.g. alkalosis) can modify the replacement solution • Regulatory issues may hinder: • Replacement solution – saline, with additives

23. Solutions: watch for errors! • Barletta et al, PediatrNephrol, 2006 • Survey: ICU, Nephrology, CRRT • 16/31 programs reported solution compounding errors with manually dispensed solutions • 2 deaths • 1 non lethal cardiac arrest • 6 seizures (hypo/hypernatremia) • 7 without complications

24. Ultrafiltration/fluid removal Rates • No Study has identified effective, safe UF rates in Children. • General acceptance that 1-2ml/kg/hr is often safe (stable patient) • Choose UF rate to: • - balance input (e.g. boluses, citrate, calcium, etc) • - remove excess fluid over time • - “make room” for IV fluids and nutrition • - Also provides solute clearance by convection

25. Ultrafiltration/fluid removal Rates • Fluid removal should be safe AND effective – no need to sacrifice one for other: • Frequent communication • Frequent reassessment (MD), Hourly reassessment (RN) • Know what the “usual hourly input is”: • IV fluids • Citrate & calcium • Nutrition (give!!) • Meds/infusions • Provide “rules” for removing “intermittent fluids” Be aware of the “outs” (tubes, urine, diarrhea) Decide desired DAILY fluid removal based on: • Haemodynamics • TOTAL severity of Fluid Overload

26. SINGLE PASS Albumin dialysis -SPAD • Removes protein bound small substances: • e.g. copper/Wilson's, drugs, toxins of liver failure • Albumin live a scavenger • Dialysis: • albumin-containing solution across highly permeable membrane • 20% albumin NOT “added” to dialysis fluid bag- it sinks however • it is mixed with normal dialysate via 3 way tap -it's “single pass” • - bags are changed • Shouldn't affect sodium – may affect (reduce) other electrolytes Collins et al, Pediatr Nephrol, 2008 Askenazi et al, Pediatrics, 2004 Ringe, Pediatr Crit Care Med, 2011

28. ANTICOAGULATION

29. ANTICOAGULATION-Points to consider • Choice of anticoagulant • Dose • Route of delivery – systemic, into the circuit

30. Anticoagulation • Heparin • Citrate • Prostacyclin

31. Dosing and Route • Heparin – 10-20 U/kg/hour • Prostacyclin – 2-8 ng/kg/min • Citrate – separate protocol • All anticoagulants to be used pre-filter with post filter monitoring ( ACT in heparin, ionised Ca in citrate)

32. Drug Dose Alteration • Drug dosing- important ( antibiotics, anticonvulsants, sedation, inotropes) • Hepatic failure + CRRT – Bigger issues • Based on: • Protein Binding Information • Volume of Distribution • Molecular Weight

33. Drug Prescribing in Renal Failureedited by George Aronoff et al • Commonly carried text by pharmacists • http://www.kdp-baptist.louisville.edu/renalbook/ • New edition to come out soon • Recommendations for new drugs • IHD and CRRT recommendations • Pediatric recommendations (T bunchman)

34. Summary • Blood flow: balance access/circuit life with tolerability • Solutions: Many choices • Know their content, regional rules, CRRT type used • Decide on desired flexibility • Decide what's best for your institution (volume, expertise) • Bicarbonate and calcium are most substantial differences • Be aware of errors – can be life threatening • Dialysis/replacement fluid rates: ie clearance dose • Balance desired clearance with undesired losses • 2-2.5 L/hour/1.73msq – suggested only • Ultrafiltration rate: • Frequent reassessment, team + targeted fluid removal decisions • Safety AND efficacy are feasible

35. Acknowledgements • T Bunchman • pCRRT Foundation • CRRT team at King’s