03/19/2019. Michael Zappitelli, MD, MSc Hospital for Sick Children, Toronto. Symposium on Pediatric Dialysis, ADC, Dallas, 2019

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1 Michael Zappitelli, MD, MSc Hospital for Sick Children, Toronto Symposium on Pediatric Dialysis, ADC, Dallas, 2019 Baxter: Reimbursed for a CRRT workshop to PICU nurses Slides: S. Goldstein D. Askenazi J. Symons E. Harvey Possibly others. Achieves what PD and HD: Effective control of uremia, lytes, acidosis, toxin removal Better tolerated than HD with hemodynamic instability Precise Volume control/immediately adaptable What you want, when you want it, including nutrition Allows heparin avoidance Possible to teach large numbers of nurses Promote nephro-icu co-management Vascular access, expertise maintenance, need for regular volume 1

2 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 2 yo boy, CLD, acute liver failure AKI, fluid overload, encephalop, coaggulop ++ bld products, pressors Solute removal Fluid removal 4 mo girl post-op heart: AKI, severe fluid overload, heart failure On pressors, going to start ECMO 3 do, severe hypernatremia AKI, Encephalopathic Given hypertonic saline for Na+ drop 8 do, hyperammonemia Encephalopathic Intubated, nutrition started Both 5 yo, Wilson s disease Severe copper rise in blood 13 yo, toxic ingestion Low GCS, lyte abnormalities Intubated Diffusion/convection, nomenclature, machines: Basics Prescription: a few decisions right away Access CRRT type & Filter Blood prime Solutions Anticoagulation Prescription: other Blood flow Clearance: dialysis & replacement solution rates Fluid removal: ultrafiltration rate Other: Drugs, Complications 2

3 CVVH CVVHDF PRE-dil POST-dil CVVHD 3

4 Extracorporeal volume 27ml Blood flow 5-50 ml/min Tiny filter Can use tiny catheter Extracorporeal volume 33ml Blood flow ml/min Extracorporeal volume 13ml Blood flow 20 ml/min Used with 3-lumen 4.5 Fr cath Prescribing CRRT 2. Decide on type 1. Access 3. Choose filter 4. Decide on blood prime 5. Choose solutions 6. Blood flow Clearance Fluid removal 7. Anticoagulation A few decisions right away 2. Decide on type 1. Access 3. Choose filter 4. Decide on blood prime 5. Choose solutions 7. Anticoagulation 4

5 Downtime from clotted circuits-access is time off therapy IJ Very accessible Large caliber (SVC) Great flows Low recirculation rate Risk for Pneumothorax Cardiac monitoring may take precedence. Femoral Usually accessible Smaller than SVC Flows may be diminished by: Abdominal Pressures Patient movement Risk for retroperitoneal hemorrhage Higher recirculation rate VASCULAR ACCESS Weight Acute Catheter < 5 kg 6.5 F Gam Cath 5- <15 kg 8 F Gam Cath 15- <35 (40) kg 10 F Quinton Mahurkar (12 and 15 cm) 35 (40) kg 11.5 F Quinton Mahurkar (13.5, 15, 16 cm) Weight Tunneled Catheter PATIENT SIZE CATHETER SIZE & SITE OF INSERTION < 5 KG 8 F Medcomp DL SOURCE 5- <20 KG Know 10 F Medcomp the catheters you NEONATE havesingle-lumen 5 Fr (COOK) Femoral artery or vein Dual-Lumen 7.0 French Femoral vein 20- < 35 KG 12 F Medcomp (COOK/MEDCOMP) 35 KG Palindrome 3-6 KG Dual-Lumen 7.0 French Internal/External-Jugular, Have a Bioflow small, Duramax medium, large option (COOK/MEDCOMP) Subclavian or Femoral vein Triple-Lumen 7.0 Fr Internal/External-Jugular, (MEDCOMP) Subclavian or Femoral vein 6-30 KG Dual-Lumen 8.0 French Internal/External-Jugular, (KENDALL, ARROW) Subclavian or Femoral vein Check position>15-kg Dual-Lumen 9.0 French Internal/External-Jugular, (MEDCOMP) Subclavian or Femoral vein >30 KG Dual-Lumen 10.0 French (ARROW, KENDALL) >30 KG Triple-Lumen 12.5 French (ARROW, KENDALL) Internal/External-Jugular, Subclavian or Femoral vein Internal/External-Jugular, Subclavian or Femoral vein 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter 5

6 A few decisions right away 2. Decide on type Still no good evidence that CVVHD better than CVVH better than CVVHDF, etc Be consistent within your centre, BUT Be ready to ADAPT e.g.: may want to clear a larger toxin (may prefer CVVH) CVVHDF: both, easy to turn one off Not much more work 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter CVVHDF 6

7 A few decisions right away 3. Choose filter 4. Decide on blood prime Will depend on machine you use Know your filters and keep them stocked E.g., ST filters (coated AN69): Small: 60 ml Medium: 93 ml E.g., HF filters (more biocompatible) Small: 60 ml Large: 165 ml Large: ~165 ml There are others All ETO sterilized Rule of thumb: keep ECV < 10% BLOOD PRIME What is blood volume? Blood volume = 100 ml/kg 0-1 mo 80 ml/kg < 16 yrs 70 ml/kg > 16 yrs Borderline ECV, unstable ++: 5% albumin 7

8 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter CVVHDF 15kg: 80ml/kg X15kg=1200 ml large ST: 14% ECV NO medium ST : 7.5% - YES. No blood prime A few decisions right away 5. Choose solutions What PO4 and K+ wanted? Anything else? Solutions vary in composition Sodium ~140 mmol/l, Cl- ~ (depends on other anions) Magnesium: 1 to 1.5 meq/l Base: Lactate: 0 to 3 meq/l, meq/l if lactate buffer Bicarbonate: 32 meq/l, 22 meq/l (this one is newish) Other: Glucose/Dextrose: 0 to 110 mg/dl Calcium: 0 to 3.5 meq/l 0 calcium if using citrate anticoagulation e.g., Prism0Cal has no calcium Potassium: 0 4 mmol/l (want to have range option or can add) Potassium, phosphate and magnesium WILL drop 8

9 YES: to avoid to fast a change in Na+ Severe hyponatremia or hypernatremia Adding Na: we are used to that Lowering sodium: Less used to Adding sterile water to the bag PHARMACY TO PREP SAFER 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter CVVHDF 15kg: 80ml/kg X15kg=1200 ml large ST: 14% ECV NO medium ST : 7.5% - YES. No blood prime K+ is 6.1 will use a K0 solution P is 2.0 mmol/l will start with no phos add I will do citrate anticoag will use 0 Ca++ sol 9

10 Heparin acts in conjunction with ATIII on thrombin and F IX, FX, FXII PATIENT & CIRCUIT AG Generally: Bolus + cont unfusion Monitor ACT: secs depends on patient & blood flow Citrate: Binds calcium, needed for each event in the cascade CIRCUIT AG Make circuit blood low Ca ++ Give calcium to PATIENT (so patient Ca ++ doesn t drop) Monitor CIRCUIT & PATIENT ica ++ Keep circuit ica ++ ~ mmol/l Other options: No AG pre-filter saline infusions Prostacyclin LMWH Rate: ~ 1.5 X blood flow (but in ml/hour!) Calcium: 0.4 X citrate rate, ideally in separate central line Change blood flow will need to change citrate rate Change citrate, need to change calcium Alkalosis 1 mmol Citrate to 3 mmol HCO3 High bicarb containing solutions exacerbate Hypernatremia Tri-Sodium Citrate infusion especially, less with ACD-A Hypocalcemic Citrate accumulation Often with liver dysfunction Babies Binding calcium so IONIZED DROPS, but TOTAL RISES. So we look at ratio. If total Ca >2.5-2,8, worry. Can give increased anion gap acidosis (liver/muscle/ kidney failure citrate not fully metabolized to HCO3) 10

11 Increase clearance (e.g., increase dialysate flow) Reduce rate check out filter Reduce blood flow Turn off briefly, restart lower rate Run acidic normal saline as post-filter fluid or replacement fluid (watch for electrolyte problems), if alkalosis is the problem 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter CVVHDF 15kg: 80ml/kg X15kg=1200 ml large ST: 14% ECV NO medium ST : 7.5% - YES. No blood prime K+ is 6.1 will use a K0 solution P is 2.0 mmol/l will start with no phos add I will do citrate anticoag will use 0 Ca++ sol Has DIC; mild-mod liver enzyme elevation Will use citrate anticoag Will not use ++high blood flows if don t have to I have a separate central line for the IV Ca++ OUTLINE: Prescribing CRRT ACD-A: will run pre-filter IV Calcium infusion 11

12 OUTLINE: Prescribing CRRT 6. Blood flow Clearance Fluid removal No set perfect rates Blood flow rate From 2 to ~10 ml/kg/min, depending on age: Neonates Reasons ~5 to 12 you ml/kg/min may change blood flow during treatment Children 4 to 8 ml/kg/min Access problems e.g., may need to reduce Older 2 to 4 ml/kg/min TMP getting high: may want to increase, less clotting in filter Most not > 200 ml/min: GENERALLY not dangerous just not necessary Increasing If citrate citrate anticoagulation accumulation: higher may blood want flow to decrease = higher = citrate less citrate need needs 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter CVVHDF 15kg: 80ml/kg X15kg=1200 ml large ST: 14% ECV NO medium ST : 7.5% - YES. No blood prime K 6.1 will use a K0 solution P 2.0 mmol/l will start with no phos add I will do citrate anticoag will use 0 Ca++ Has DIC; mild-mod liver enzyme elevation Will use citrate anticoag Will not use high blood flows if don t have to I have a separate central line for the IV Ca++ Started blood flow at 60 ml/min: balance citrate & circuit life TMP began to rise/little clots: increased to 80 ml/min 12

13 Clearance Clearance mostly a function of: Dialysis fluid flow rate Qd + Qr (CVVHDF) Replacement fluid flow rate Don t forget the post-dilution (that ml oblig post) 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,drug clearance = more CITRATE clearance = more work = more risk for rapid shifts Lower rates simplify electrolyte balance and limit protein loss No well-defined right dose of clearance. Standard suggestion: Qd or Qr or Qd+Qr ~ ml/kg/hour OR 2 to 2.5 liters/hr/1.73msq E.g.,: K is 8 with ECG changes when we start Makes sense to start at higher clearance initially, right? Can do 4-6 L/hr/1.73msq Consider complication of dialysis disequilibrium syndrome Consider clearance of other things 13

14 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter Started blood flow at 60 ml/min: balance citrate & circuit life TMP began to rise/little clots: increased to 80 ml/min CVVHDF 15kg: 80ml/kg X15kg=1200 ml large ST: 14% ECV NO medium ST : 7.5% - YES. No blood prime K 6.1 will use a K0 solution P 2.0 mmol/l will start with no phos add I will do citrate anticoag will use 0 Ca++ K6.1 and no ECG changes Worry about Abx clearance Standard solute clearance Has DIC; mild-mod liver enzyme elevation Will use citrate anticoag Will not use high blood flows if don t have to I have a separate central line for the IV Ca++ OUTLINE: Prescribing CRRT ~1.1 L/1.73m2/hour ~1.1 L/1.73m2/hour Universally safe UF rates in children unknown General rule: 1-2ml/kg/hr can be safe in a stable patient Critically ill: try to aim < ~3% body weight/day Critically ill but really stable: avoid >4-5% BW per day Want safety AND achieve fluid removal goal no need to sacrifice one: Frequent communication: Not achieving goal, why? Need more vasopressors to achieve goal? Frequent reassessment (MD), Hourly (RN) 14

15 Machine takes care of fluids in run by the machine (e.g., post-filter replacement, citrate if using machine to run citrate) Know what the usual hourly input is, as this is what you need to tell machine to remove to keep patient fluid balance even :» IV fluids» Citrate & calcium» Nutrition (give!!)» Meds/infusions Be aware of the outs (tubes, urine, diarrhea) account for How to approach? How negative should I aim the patient to be per hour? 1. Know where you are starting: total FO% - what is overall fluid removal goal?? Is resp status/heart function compromised? FO% = urgency /how bad off are we? Actual volume overload (liters): more about your target goal 2. Decide desired DAILY fluid removal goal: what is safe? i.e. what volume is <3-5% weight per day/i.e., upper safety limit? hrs: That s the ~upper limit of hourly negative balance Is this 1-2 ml/kg/hour? i.e., is it safe? 4. Nephro-PICU agree on hourly fluid removal 5. Do what you can to make easier to remove fluid?should we increase pressors??should we consider 25% Albumin infusion?? Are we being too aggressive? 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter CVVHDF 15kg: 80ml/kg X15kg=1200 ml large ST: 14% ECV NO medium ST : 7.5% - YES. No blood prime K 6.1 will use a K0 solution P 2.0 mmol/l will start with no phos add I will do citrate anticoag will use 0 Ca++ Has DIC; mild-mod liver enzyme elevation Will use citrate anticoag Will not use high blood flows if don t have to I have a separate central line for the IV Ca++ Started blood flow at 60 ml/min: balance citrate & circuit life TMP began to rise/little clots: increased to 80 ml/min K6.1 and no ECG changes 3L+ ~20% FO, ++edema; unstable 3% BW = Worry 15X0.03= about Abx450mL/day clearance Standard solute clearance 450/24 = 18 ml/hr Decide start with ml/hr Increase pressors Non-machine ins = 150 ml/hour 10 ml/hr OUT from CT UFR: (150-10)+15 (neg)=155 ml/hr 15

16 Also Drugs Complications Use drug characteristics and type/amount of clearance. High VoDistr (>0.7-1L/kg = distributed ++ to non vascular compartments) may still get some clearance with long therapies Low water-solubility High protein binding (>60-80%) Large molecules (>60-80 kda) generally lower clearance CVVHD NOT EQUAL TO CVVH!!!! Old but useful article: Veltri et al, Pediatric Drugs, 2004 CRRT cessation: Do we need to restart? Reassess this every time the circuit stops. Is the patient stable enough to restart? Has the urine output changed? 16

17 Access problems HD/CRRT: See increase negative (access) or positive (return) pressures. Assure adequate sedation Check kinks Pause and flush/pull access. May need to reverse lines assure citrate still going in right place! May need tpa Aggressive ultrafiltration Shouldn t happen Can kill small children Hypothermia Especially small children: Prevent, don t wait. Dialysate line warmers Return blood line warming Patient heat lamps. Bleeding really common, often due to underlying disease. Too fast clearance (e.g., chronic-semi-chronic high urea) Rapid sodium changes with hypo/hypernatermia Seizures Citrate issues Thrombosis from catheter Blood loss 17

18 AN 69 membrane, banked blood, acidosis Severe hemodynamic instability at start of circuit Prevention: correction of acidosis in patient and/or circuit Calcium Avoid blood prime Make complications monitoring part of the orders 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 10Fr tunneled catheter CVVHDF 15kg: 80ml/kg X15kg=1200 ml large ST: 14% ECV NO medium ST : 7.5% - YES. No blood prime K 6.1 will use a K0 solution P 2.0 mmol/l will start with no phos add I will do citrate anticoag will use 0 Ca++ Has DIC; mild-mod liver enzyme elevation Will use citrate anticoag Will not use high blood flows if don t have to I have a separate central line for the IV Ca++ Started blood flow at 60 ml/min: balance citrate & circuit life TMP began to rise/little clots: increased to 80 ml/min K6.1 and no ECG changes Worry about Abx clearance Standard solute clearance 3L+ ~20% FO, ++edema; unstable 3% BW = 15X0.03= 450mL/day 450/24 = 18 ml/hr I decide start with neg 15 ml/hr Increase pressors Non-machine ins = 150 ml/hour 10 ml/hr OUT from CT UFR: (150-10)+15 (neg)=155 ml/hr Access pressure issues: MRI tpa Citrate accumulation: increased dialysis & decreased blood flow (antibiotics not cleared by D) Colleague increased neg to 100 ml/hr - STOP 18

19 CRRT: has specific advantages over other RRT s Prescription/performing: Some decisions need to be made right away, some not Good access is crucial, know your options CRRT type: no data on what is better. Choose one. Stick to it. Be ready to adapt. This of the type of solute clearance you are doing and if it matters Extracorporeal volume: Minimize, may need blood prime Consider hemodynamic stability of patient. Choose a method and stick to it. Know and choose solutions: Citrate anticoagg 0 calcium K, PO4, can be adapted Anticoagulation Prescription/performing Blood flow: maximize stability + minimize clotting Clearance: D + R fluid rate. They both remove small solutes. ~2-2.5 L/1.73msq/hour May need higher in certain situations Ultrafiltration: Water removal. Have a plan. Total goal, Daily goal (safety), Hourly goal Frequent reassessment & communication Drugs: Need to redose? Are they being cleared? Do I need to change my clearance method? Complications: Anticipate Ensure monitoring is part of the orders 19

20 Thank you S Goldstein, D Askenazi, D Selewski, G Fleming, P Brophy, T Bunchman, A Deep, M Paden, R Basu, A Arikan, B Bridges, D Cooper, E Harvey michael.zappitelli@sickkids.ca HD Qb: 70 ml/min! 2.8 kg baby Access technical issues 2 neonates with UCD Pre-CRRT NH3>1000 umo/l CVVHD: ~8 L/1.73msq/hour 50% NH3 reduction: hrs NH3 <200 umol/l: 2-6 hrs 20

21 See protocol on i-share In general: Start high clearance (4-6L/1.73msq/hr) if Evidence of other osmole (high serum osm) maybe start with 2L/1.73msq, then increase Follow NH3 (or toxin): when happy, progressively decrease Clearance keep checking ammonia/toxin hold clearance Stop Communicate with metabolomics and PICU: Is there ongoing catabolism? Have we increased metabolic meds? (they are cleared?) Feeding adequate/correct? Make sure other meds correctly dosed!!!! Prime circuit with blood (reconstitute with NaHCO3/0.9%NS), e.g., 1:1 Give PRBCS at same time and rate as bled onto circuit Prime circuit with blood and `dialyze` 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 Collins et al, Pediatr Nephrol, 2008 Askenazi et al, Pediatrics, 2004 Ringe, Pediatr Crit Care Med,

22 4 yo boy with severe GAS infection: AKI, fluid overload, in shock On antibiotics & pressors 4 mo girl post-op heart: AKI, severe fluid overload, heart failure On pressors, going to start ECMO 2 yo boy, CLD, acute liver failure AKI, fluid overload, encephalop, coaggulop ++ bld products, pressors 3 do, severe hypernatremia AKI, Encephalopathic Given hypertonic saline for Na+ drop 8 do, hyperammonemia Encephalopathic Intubated, nutrition started 5 yo, Wilson s disease Severe copper rise in blood 13 yo, toxic ingestion Low GCS, lyte abnormalities Intubated 22