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CRRT Prescription

Akash DeepDirector - PICU

King’s College HospitalLondon

ChairRenal/CRRT Section

European Society of Pediatric and Neonatal Intensive Care (ESPNIC)

Vascath – Size , location

Rates & Dose

Blood flow

Dialysis fluid

Replacement fluid

Ultrafiltration rate

Anticoagulation

Drug Dose

Suggested

Not necessarily a recipe

Overview

• 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!!!!

Is there a “typical” 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

Essential steps in CRRT Prescription

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

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

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

Blood flow rate

Treatment 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)

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: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: REALIZE: What you prescribe is not necessarily what the patient gets!!Time off circuit, microclots in filter over time, predilution

Urea clearance ~ 30-40 ml/min/1.73msq

Dialysis and Replacement Fluid Rates: Clearance & Dose

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

CVVHCVVHQr = 300 Qr = 300 ml/hourml/hour

CVVHDCVVHDQd = 300 ml/hourQd = 300 ml/hour

CVVHDFCVVHDFQd = 150ml/hour Qd = 150ml/hour Qr = 150 ml/hourQr = 150 ml/hour

10 kg child: 30 ml/kg/hr “clearance” OR ~ 0.26 msq: 2L/1.73msq/hour = 300

ml/hour

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

425 patientsEndpoint = survival 15 days after D/C HF

146 UF rate 20ml/kg/hrsurvival significantly lower

in this group compared to the others

139 UF rate 35ml/kg/hrp=0.0007

140 UF rate 45ml/kg/hrp=0.0013

ATN Study

Randomised Evaluation of Normal vs Augmented Level Replacement (RENAL) Therapy )

1500 critically ill adultsCVVHDF25 ml/kg/hour40 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.

• 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

Does the dose of solution exposure per unit of time matter

• 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

So

• 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

and

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).

Solutions

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

Dialysis fluid? Replacement fluid?

Barletta et al, Pediatr Nephrol, 2006 Barletta et al, Pediatr Nephrol, 2006

Survey: ICU, Nephrology, CRRT16/31 programs reported solution compounding errors with manually dispensed solutions2 deaths1 non lethal cardiac arrest6 seizures (hypo/hypernatremia)7 without complications

Solutions: watch for errors!

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

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

Ultrafiltration/fluid removal Rates

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, 2008Askenazi et al, Pediatrics, 2004

Ringe, Pediatr Crit Care Med, 2011

SINGLE PASS Albumin dialysis -SPAD

ANTICOAGULATION

• Choice of anticoagulant

• Dose

• Route of delivery – systemic, into the circuit

ANTICOAGULATION-Points to consider

• Heparin

• Citrate

• Prostacyclin

Anticoagulation

• 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)

Dosing and Route

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

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)

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

Summary

• T Bunchman

• pCRRT Foundation

• CRRT team at King’s

Acknowledgements