Pediatric CRRT The Prescription: Rates, Dose, Fluids Michael Zappitelli, MD, MSc Montreal Children's Hospital McGill University Health Centre

Not necessarily a recipe Overview Rates & Dose Blood flow Dialysis fluid Replacement fluid Ultrafiltration rate Fluids Suggested Not necessarily a recipe

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 May be machine – dependent Prisma: 180 ml/min Prismaflex & Aquarius: 450 ml/min Start lower and increase by about 10 minutes (?)

Blood flow rate No set “perfect rates” From 3 to ~10 ml/kg/min, depending on age: 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: Be aware of access and return pressure Visually inspect filter for clots Transmembrane pressure – may need to increase blood flow Filtration fraction

Solutions Slow continuous ultrafiltration – none CCVHD – dialysis fluid for diffusive clearance CVVH – replacement fluid: replacing fluid you are removing to achieve solute clearance by convection CVVHDF – both Using these to correct metabolic abnormalities (remove) and prevent treatment-related metabolic abnormalities (replace).

Ideal solutions Composition: Bicarbonate: Calcium: Physiological/ compatible Reliable Inexpensive Easy to prepare Simple to store Quick to the bedside Widely available Composition: Sodium: ~ 130 to 140 Chloride: ~105 to 120 dependent on other anions (HCO3) Potassium: MOST Zero – need to add (some have) Magnesium: 1 to 1.5 mEq/L Glucose/Dextrose: 0 to 110 mg/dL Lactate: Most 0 to 3 mEq/L (35-40 mEq/L if lactate buffer) Peritoneal dialysis fluid? Hyperglycemia, metab acidosis Soysal et al, Ped Neph, 2007 Pre-made IV solutions: Saline, Lactated Ringers Multi-bag systems: why? Custom-made solutions: Local pharmacy; outsource Commercially available solutions: Ready-bags (compartments) Concentrate added to bag Bicarbonate: Most 30-35 mEq/L Few ZERO As low as 22 to 25 mEq/L Calcium: 0 to 3.5 mEq/L

Some solutions are more flexible than others Choosing solutions Cost (Storing, frequency of use) Anticoagulation: +/- calcium with citrate anticoagulation There are citrate based solutions and data Patient safety – patient volume? Does everyone prescribing really understand? Regulatory issues (dialysis versus replacement fluid....) Some solutions are more flexible than others Accusol Prismasate Normocarb Hemosol BO Duosol Prismasol ...........

Phosphate They WILL develop hypophosphatemia Can replace: IV boluses, TPN MANY add it to solutions – but no good data Worry about precipitation, calcium-magnesium binding How much too much? No good answer. Many 1.2-1.5 mmol/L Pharmacy versus nurse-based addition?

Troyanov et al, Intens Care Med, 2004 Retrospective clinical Adding Phosphate Troyanov et al, Intens Care Med, 2004 Experiment Added 1.2 mmol/L PO4- to calcium – rich solutions 5 hours: no effect on calcium, bicarb, pH, pCO2 No visual precipitation With and without filtering 2 days: to precipitation Retrospective clinical 14 adults CVVHDF KPO4 added when <1.5 mmol/L (protocolized) No negative effects caused on calcium, bicarb, pH Santiago et al, Therap Apher & Dialysis, 2010 Experiment Added NaPO4 to dialysis/replacement fluid bags (12) containing calcium and magnesium 0.8 mmol/L 1.5 mmol/L 2.5 mmol/L No change in calcium, magnesium, sodium, gluc, pH 2, 24 and 48 hours Consideration: Most dialysis or replacement fluid bags will not need to be hung for more than a day Santiago et al, KI, 2009 Experiment Pre-post evaluation of adding NaPO4 to dial & replace solution 0.8 mmol/L, 47 children, solutions contained Ca++ & Mg++ No precipitation seen Less IV PO4 needed

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

Albumin dialysis 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 25% albumin “added” to dialysis fluid bag: 2-5% albumin solution it's “single pass” - bags are changed Shouldn't affect sodium – may affect (reduce) other electrolytes Theoretically may affect citrate anticoagg rates Allergic reaction Collins et al, Pediatr Nephrol, 2008 Askenazi et al, Pediatrics, 2004 Ringe, Pediatr Crit Care Med, 2011

Solutions: watch for errors! Barletta et al, Pediatr Nephrol, 2006 Survey: ICU, Nephrology, CRRT 16/31 programs reported solution compounding errors 2 deaths 1 non lethal cardiac arrest 6 seizures (hypo/hypernatremia) 7 without complications Soysal et al, Pediatr Nephrol, 2007 Country where resources dictate need to use PD solution for dialysis and NS + additives for replacement fluid Many reported electrolyte complications: glucose, sodium, acidosis

Dialysis and Replacement Fluid Rates: Clearance & Dose Clearance mostly a function of: Dialysis fluid flow rate (Qd) Replacement fluid flow rate (Qr) Higher rates = higher clearance for IEM, drug removal, severe high K = more middle molecule clearance (CVVH/CVVHDF) = more hypophosphatemia, kalemia, magnesemia = more amino acid losses = more drug clearance = more CITRATE clearance = more work to change bags, give electrolyte infusions Lower rates simplify electrolyte balance and limit protein loss 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: Qd or Qr or Qd+Qr ~ 20-40 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 ~ 30-40 ml/min/1.73msq

10 kg child: 30 ml/kg/hr “clearance” OR ~ 0. 26 msq: 2L/1 10 kg child: 30 ml/kg/hr “clearance” OR ~ 0.26 msq: 2L/1.73msq/hour = 300 ml/hour CVVH Qr = 300 ml/hour CVVHDF Qd = 150ml/hour Qr = 150 ml/hour CVVHD Qd = 300 ml/hour

Ultrafiltration/fluid removal Rates 1717 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

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) – account for

Ultrafiltration/fluid removal Rates Decide desired DAILY fluid removal, after understanding TOTAL severity of Fluid Overload Assure safety of this desired daily fluid removal Decide desired hourly “negative balance” Even balance?: Simply remove hourly ins – significant outs Negative balance?: Same + remove desired negative balance Think about filtration fraction – make sure not too high UFR/Plasma flow rate --- UFR/Qb <20-25% CVVHD or post-filter CVVH <30-35% pre-filter CVVH

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 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