0. CRRT Prescription Akash Deep Director - PICU King’s College Hospital London Chair Renal/CRRT Section European Society of Pediatric and Neonatal Intensive Care (ESPNIC)

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

2. 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!!!!

3. 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

4. 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

5. 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: ml/min
11-20kg: ml/min
21-50kg: ml/min
>50kg: ml/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

6. 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

7. Treatment Dose

8. 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)

9. Dialysis and Replacement Fluid Rates: Clearance & Dose
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 ~ 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
Urea clearance
~ ml/min/1.73msq

10. 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 (2);r57

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

12. Dialysis Dose and Outcome Ronco et al. Lancet 2000; 351: 26-30
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
Conclusions:
Minimum UF rates should be ~ 35 ml/kg/hr
Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration

14. ATN Study

16. 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.

17. 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

18. 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 /mls/hr/1.73m2

19. 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

20. 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).

21. 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

22. Solutions: watch for errors!
Barletta et al, Pediatr Nephrol, 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

23. Ultrafiltration/fluid removal Rates
2323
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

24. 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

25. 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

27. ANTICOAGULATION

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

29. Anticoagulation
Heparin
Citrate
Prostacyclin

30. 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)

31. 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

32. Drug Prescribing in Renal Failure edited by George Aronoff et al
Commonly carried text by pharmacists
New edition to come out soon
Recommendations for new drugs
IHD and CRRT recommendations
Pediatric recommendations
(T bunchman)

33. 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

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