1. Acute Renal Replacement Therapy for the Infant Jordan M. Symons, MD University of Washington School of Medicine Children’s Hospital & Regional Medical Center Seattle, WA jordan.symons@seattlechildrens.org

2. Objectives Indications and goals for acute renal replacement therapy Modalities for renal replacement therapy –Peritoneal dialysis –Intermittent hemodialysis –Continuous renal replacement therapy (CRRT) Special issues related to the infant

3. Indications for Renal Replacement Volume overload Metabolic imbalance Toxins (endogenous or exogenous) Inability to provide needed daily fluids due to insufficient urinary excretion

4. Goals of Renal Replacement Restore fluid, electrolyte and metabolic balance Remove endogenous or exogenous toxins as rapidly as possible Permit needed therapy and nutrition Limit complications

5. Renal Replacement for the Infant: A Set of Special Challenges Small size of the patient Equipment designed for larger people Small blood volume will magnify effects of any errors Achieving access may be difficult Staff may have infrequent experience

6. Modalities for Renal Replacement Peritoneal dialysis Intermittent hemodialysis Continuous renal replacement therapy (CRRT)

7. Modalities for Renal Replacement Peritoneal dialysis Intermittent hemodialysis Continuous renal replacement therapy (CRRT)

8. PD: Considerations for Infants ADVANTAGES Experience in the chronic setting No vascular access No extracorporeal perfusion Simplicity ? Preferred modality for cardiac patients? DISADVANTAGES Infectious risk Leak ? Respiratory compromise? Sodium sieving Dead space in tubing

9. H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2OH2OH2O Sodium Sieving: A Problem of Short Dwell PD Na + H2OH2O Result: Hypernatremia

10. Dead Space: A Problem with Low Volume PD

11. Modalities for Renal Replacement Peritoneal dialysis Intermittent hemodialysis Continuous renal replacement therapy (CRRT)

12. IHD: Considerations for Infants ADVANTAGES Rapid particle and fluid removal; most efficient modality Does not require anticoagulation 24h/d DISADVANTAGES Vascular access Complicated Large extracorporeal volume Adapted equipment ? Poorly tolerated

13. Modalities for Renal Replacement Peritoneal dialysis Intermittent hemodialysis Continuous renal replacement therapy (CRRT)

14. Pediatric CRRT: Vicenza, 1984

15. CRRT for Infants: A Series of Challenges Small patient with small blood volume Equipment designed for bigger people No specific protocols Complications may be magnified No clear guidelines Limited outcome data

16. Potential Complications of Infant CRRT Volume related problems Biochemical and nutritional problems Hemorrhage, infection Thermic loss Technical problems Logistical problems

17. CRRT in Infants <10Kg: Outcome Patients <10kgPatients 3-10kgPatients <3kg 38% Survival 41% Survival 25% Survival Am J Kid Dis, 18:833-837, 2003

18. ppCRRT Data of Infants <10Kg: Demographic Information Number of Subjects84 (51 boys (61%)) (33 girls (39%)) AgeMedian 69 days (1 d - 2.9 y) ICU Admit weightMedian 4.4 kg (1.3 - 10 kg)

19. ppCRRT Data of Infants <10Kg: Primary Diagnoses

20. ppCRRT Data of Infants <10Kg: Indications for CRRT Fluid Overload and Electrolyte Imbalance84% Other (Endogenous Toxin Removal)16% N=84

21. ppCRRT Data of Infants <10Kg: Clinical Data ParameterMedianRange Days in ICU prior to CRRT20 - 135 PRISM score — ICU admit17.50 - 48 PRISM score — CRRT start200 - 48 Inotrope number — CRRT start10 - 4 Urine output — CRRT start (ml/kg/hr over prior 24hrs) 0.70 - 12 % Fluid overload from ICU admission to CRRT start 13.7-28 - 220

22. ppCRRT Data of Infants <10Kg: Technical Characteristics of CRRT Catheter SiteFemoral60% Internal Jugular28% Subclavian12% ModalityCVVHD59% CVVH18% CVVHDF23% AnticoagulationCitrate55% Heparin45% PrimeBlood87% Saline8% Albumin5% N=84

23. ppCRRT Data of Infants <10Kg: CRRT Treatment Data N=84 ParameterMedianRange Blood Flow (ml/kg/min) 81.7-46 Fluid Flow (ml/kg/hour)677-571 Average CRRT Clearance (ml/hr/1.73M 2 ) 2582135-19319 Aggregate CRRT Clearance (ml/hr/1.73M 2 ) 3540135-12713 CRRT duration (days)50-83

24. ppCRRT Data of Infants <10Kg: Survival by Weight 44%42%43%64% p=0.001 p=1.0

25. ppCRRT Data of Infants <10Kg: Factors Effecting Survival Clinical VariableSurvivorsNon-SurvivorsP Admission PRISM score1621<0.05 GI/Hepatic disease8%31%0.01 Multiorgan dysfunction68%91%0.04 Pressor Dependency36%69%<0.01 Mean Airway Pressure1120<0.001 Initial urine output (ml/kg/hr)2.41.00.02 %Fluid Overload at Start15%34%0.02 >10% Overload at Start43%71%0.02

26. ppCRRT Data of Infants <10Kg: Survival by Return to Dry Weight 78% 35% 22% 65%

27. Infant CRRT at Children’s Hospital & Regional Medical Center, Seattle

28. Infant CRRT in Seattle: Overview Coordinated by nephrology Performed in infant/pediatric ICU Set up by dialysis nurses Run at the bedside by neonatology or critical care nurses Dedicated CRRT device –BM-25: 1999 – 2005 –Prisma: 2005 - present

29. CRRT Access in the Neonate: What Works? Hemodialysis Line: 7 Fr double lumen Two single lumen lines: –5 Fr catheters or introducers Umbilical lines: –5 Fr UAC; 7 Fr UVC Leg position - be creative Tape on the skin - may need to get creative

30. PRISMA Dedicated CRRT device Highly automated Designed for ease of use at the bedside

31. CRRT Filter Sets for Prisma Surface Area Priming Volume Membrane M-10*0.042m 2 50mlAN-69 M-600.6m 2 90mlAN-69 M-1000.9m 2 107mlAN-69 HF-10001.15m 2 128ml Polyarylethersulfone (PAES) * Not available in US

32. Bradykinin Release Syndrome Mucosal congestion, bronchospasm, hypotension at start of CRRT Resolves with discontinuation of CRRT Thought to be related to bradykinin release when patient’s blood contacts hemofilter Exquisitely pH sensitive

33. Bypass System to Prevent Bradykinin Release Syndrome PRBC Waste Modified from Brophy, et al. AJKD, 2001.

34. Recirculation System to Prevent Bradykinin Release Syndrome D Waste Recirculation Plan: Qb 200ml/min Qd ~40ml/min Time 7.5 min Based on Pasko, et al. Ped Neph 18:1177-83, 2003 Normalize pH Normalize K +

35. Simple Systems to Limit Likelihood of Bradykinin Release Syndrome Don’t prime on with blood Don’t use the AN-69 membrane

36. Thermal Regulation Hotline® blood warming tubing Place at venous return to patient Leave on at set temperature of 39 C Treat temp elevations if they occur

37. Infant CRRT in Seattle: CRRT Staffing Dialysis RN sets-up & initiates therapy PICU/IICU RN manages patient Nephrology/Dialysis RN on call 24/7 Acuity assigned to pump as if a separate patient Staffing determined by acuity

38. Infant CRRT in Seattle: How to Handle a Rare Procedure Developed an Acute Initiation Checklist defining specific roles/actions for: –Infant ICU MD –Nephrology MD –Infant ICU RN –Dialysis RN –IV access MD

39. Acute Initiation Checklist: Example Infant ICU Nurse Time Zero: –Move pt to room with dialysis water –Get orders from resident for IV fluids to keep access open 20 – 40 min: –Meet MD; discuss RRT plan 60 – 120 min: –Meet ICU team Dialysis Nurse 10 – 60 min: –Arrive and begin setup 20 – 40 min: –Meet MD; discuss RRT plan 60 – 120 min: –Complete prime; ready for access –Begin RRT –Meet ICU team

40. Acute Initiation Checklist: Example Nephrology MD Time Zero: –Contact dialysis nurse to start RRT urgently 10 – 20 min: –Bring catheters to ICU –Enter orders for RRT 20 – 40 min: –Meet ICU MDs & RNs, discuss plan 60 – 120 min: –Present in ICU for initiation –Meet ICU team IV Access MD 10 – 30 min: –Arrive and begin insertion of dialysis access 60 min (or when circuit is ready for Rx) –Complete insertion of access –Connect ports to heparin IV solutions

41. Infant RRT: Summary All modalities of RRT possible for infants No modality is perfect Technical challenges can be met Careful planning with institution, program, and individuals improves care Cooperation, communication, and collaboration will increase our success

42. Thanks!