RRT Choice

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  • Figure 1. Enrollment, Randomization, and Follow-up of Study Patients.
  • Table 3. Primary and Secondary Outcomes.
  • Figure 2. Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death at 60 Days, According to Baseline Characteristics (Panel B). Panel A shows the cumulative probability of death from any cause in the entire study cohort. Panel B shows odds ratios (and 95% confidence intervals [CI]) for death from any cause by 60 days in the group receiving the intensive treatment strategy as compared with the group receiving the less-intensive treatment strategy, as well as P values for the interaction between the treatment group and baseline characteristics. P values were calculated with the use of the Wald statistic. Higher Sequential Organ Failure Assessment (SOFA) scores indicate more severe organ dysfunction. There was no significant interaction between treatment and subgroup variables, as defined according to the prespecified threshold level of significance for interaction (P=0.10). Sex was not recorded for one patient receiving less-intensive therapy.
  • Table 4. Summary of Complications Associated with Study Therapy.
  • RRT Choice

    1. 1. Renal Replacement Therapy Options for Children Timothy E. Bunchman, MD Professor & Director Helen DeVos Children’s Hospital Grand Rapids, MI [email_address]
    2. 2. Questions? <ul><li>Is there an optimal form of RRT in children independent of cause of AKI? </li></ul><ul><li>Are there studies comparing outcome randomized by RRT modality in children? </li></ul>
    3. 3. RRT Options (all are reasonable to use) <ul><li>PD (continuous or intermittent) </li></ul><ul><ul><li>Acute, CAPD, CCPD </li></ul></ul><ul><li>HD (intermittent) </li></ul><ul><ul><li>Standard vs High Flux </li></ul></ul><ul><li>CRRT (continuous) </li></ul><ul><ul><li>CVVH, CVVHD, CVVHDF </li></ul></ul>
    4. 4. Dialysis (diffusive) <ul><li>PD vs. HD vs. CVVHD </li></ul><ul><ul><li>Works with solute clearance across a semi-permeable membrane </li></ul></ul><ul><ul><li>The greater the gradient the greater the clearance </li></ul></ul><ul><ul><li>The greater the solution exposure per unit of time the greater the clearance </li></ul></ul>
    5. 5. Diffusive Clearance <ul><li>CVVHD/HD/PD </li></ul><ul><li>Diffusive clearance </li></ul><ul><li>Dialysate </li></ul><ul><ul><li>Physiologic sterile solution that is infused countercurrent to the blood flow rate (Qd) </li></ul></ul>
    6. 6. Replacement (Convective) <ul><li>Due to mass transfer (push) of solute thru a semi-permeable membrane </li></ul><ul><li>The pore size of the membrane may effect clearance </li></ul><ul><ul><li>AN-69 membrane > Polysulphone </li></ul></ul><ul><li>The greater the solution exposure per unit of time the greater the clearance </li></ul>
    7. 7. <ul><li>CVVH </li></ul><ul><li>Convective clearance </li></ul><ul><li>Replacement Solutions </li></ul><ul><ul><li>Physiologic sterile solution that is either infused pre filter (NA) or post filter (outside of NA) that infused at a set rate (Qr) </li></ul></ul>Convective Clearance
    8. 8. <ul><li>CVVHDF </li></ul><ul><li>Convective clearance </li></ul><ul><ul><li>Replacement Solutions </li></ul></ul><ul><li>Diffusive clearance </li></ul><ul><ul><li>Dialysis solution </li></ul></ul>Convective and Diffusive Clearance
    9. 9. Sieving Coefficients Solute (MW) Convective Coefficient Diffusion Coefficient Urea (60) 1.01 ± 0.05 1.01 ± 0.07 Creatinine (113) 1.00 ± 0.09 1.01 ± 0.06 Uric Acid (168) 1.01 ± 0.04 0.97 ± 0.04* Vancomycin (1448) 0.84 ± 0.10 0.74 ± 0.04** Calcium (protein bound) 0.67 + 0.1 0.61 + 0.07 Cytokines (large) adsorbed minimal clearance *P<0.05 **P<0.01
    10. 10. Impact of urea Clearance CVVH vs CVVHD (Maxvold et al, Crit Care med. 2000 Apr;28(4):1161-5) <ul><li>Study design </li></ul><ul><ul><li>Fixed blood flow rate-4 mls/kg/min </li></ul></ul><ul><ul><li>HF-400 (0.3 m2 polysulfone) </li></ul></ul><ul><ul><li>Cross over for 24 hrs each to prefilter replacement fluid (CVVH) or Dx (CVVHD) flow at 2000 mls/hr/1.73 m2 </li></ul></ul>
    11. 11. Comparison of Urea Clearance: CVVH vs CVVHD (Maxvold et al, Crit Care med. 2000 Apr;28(4):1161-5) Urea Clearance (mls/min/1.73 m2) BFR = 4 mls/kg/min FRF/Dx FR = 2 l/1.73 m2/hr SAM = 0.3 m2 p = NS
    12. 12. Solute clearance vs UF <ul><li>Solute Clearance/unit of time </li></ul><ul><ul><li>HD > HF > PD </li></ul></ul><ul><ul><ul><li>(30-50 l/hr vs 2 l/hr vs 1-2 /hr Dx) </li></ul></ul></ul><ul><li>UF with regard to hemodyamics </li></ul><ul><ul><li>HF > PD > HD </li></ul></ul><ul><ul><ul><li>(24 hrs/day vs 3-4 hrs/day or QO Day) </li></ul></ul></ul>
    13. 13. Dialysis Dose Weekly stdKt/V 0.3 0.5 0.7 0.9 1.1 1.3 1.5 eKt/V each dialysis No. of Days/week Adapted from Gotch et al. Kidney Int 2000;58:S3-18 PD 0 1 2 3 4 5 6 7 8 9 10 2 3 4 5 6 7 EDD 35ml/kg 45ml/kg 20ml/kg CRRT
    14. 14. Dialysis Dose and Outcome Ronco et al. Lancet 2000; 351: 26-30 <ul><li>Conclusions: </li></ul><ul><ul><li>Minimum UF rates should be ~ 35 ml/kg/hr </li></ul></ul><ul><ul><li>Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration </li></ul></ul>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
    15. 15. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD, and PD <ul><li>Variable CRRT IHD PD </li></ul><ul><li>---------------------------------------------------------------------------------------------- </li></ul><ul><li>Continuous RRT + - + </li></ul><ul><li>Hemodynamic stability + - + </li></ul><ul><li>Fluid balance achievement + - - </li></ul>
    16. 16. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD, and PD <ul><li>Variable CRRT IHD PD </li></ul><ul><li>---------------------------------------------------------------------------------------------- </li></ul><ul><li>Unlimited nutrition + - - </li></ul><ul><li>Superior metabolic control + - - </li></ul><ul><li>Continuous removal of toxins + - + </li></ul><ul><li>Simple to perform ± - + </li></ul>
    17. 17. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD and PD cont. <ul><li>Variable CRRT IHD PD </li></ul><ul><li>--------------------------------------------------------------------------------------- </li></ul><ul><li>Stable intracranial pressure + - + </li></ul><ul><li>Rapid removal of poisons - + - </li></ul><ul><li>Limited anticoagulation -/+ + + </li></ul>
    18. 18. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD and PD cont. <ul><li>Variable CRRT IHD PD </li></ul><ul><li>---------------------------------------------------------------------------------------------- </li></ul><ul><li>Intensive care nursing support + - + </li></ul><ul><li>Hemodialysis nursing support ± + + </li></ul><ul><li>Patient mobility - + - </li></ul>
    19. 19. PATIENT MORTALITY Percent of Patients (%) Modality (NS in mortality) N=21 N=9 N=12 Fleming et al., J Thorac Cardiovasc Surg, 1995
    20. 20. CALORIC INTAKE PD CAVH * CVVH * Fleming et al., J Thorac Cardiovasc Surg, 1995 % Change From Baseline Modality(* p < 0.05 compared to PD)
    21. 21. Renal Replacement Therapy in the PICU Pediatric Outcome Literature <ul><li>122 children studied </li></ul><ul><li>No PRISM scores </li></ul><ul><li>Most common diagnosis </li></ul><ul><ul><li>IHD: primary renal failure </li></ul></ul><ul><ul><li>CRRT: sepsis </li></ul></ul><ul><ul><ul><li>31% survival </li></ul></ul></ul><ul><li>Conclusion: patients who receive CRRT are more ill </li></ul>Maxvold NJ et al: Am J Kidney Dis 1997 Nov;30(5 Suppl 4):S84-8
    22. 22. Pediatric ARF: Modality and Survival % Survival Ped Neph 16:1067-1071, 2001 P<0.01 P<0.01 (ns)
    23. 23. Pediatric ARF: Modality and Survival <ul><li>Patient survival on pressors (35%) lower than without pressors (89%) (p<0.01) </li></ul><ul><li>Lower survival seen in CRRT than in patients who received HD for all disease states </li></ul>Ped Neph 16:1067-1071, 2001
    24. 24. Unique Situations-PD <ul><li>Infants and Post Op Hearts </li></ul><ul><ul><li>Ease of fluid management </li></ul></ul><ul><ul><ul><li>Chien et al Pediatr Neonatol 2009; 50:25-279 </li></ul></ul></ul><ul><ul><li>Ease of administration at bedside </li></ul></ul><ul><ul><ul><li>Bonillis-Felix PDI 2009 29 S183-185 </li></ul></ul></ul><ul><li>Limited resources </li></ul>
    25. 25. The etiology of acute renal failure- Nigeria ( Anochie & Eke Peds Neph 2005:20 1610-1614) Etiology Number (%, N =211) Gastroenteritis 61 (28.9) Septicaemia 32 (15.2) With Tetanus 4 (5.3) Acute glomerulonephritis 29 (13.7) Plasmodium falciparum malaria 29 (13.7) Birth asphyxia 27 (12.8) Haemolytic uraemic syndrome 7 (3.3) Malignancy 6 (2.8) Leukaemia 4 Burkitt lymphoma 2 HIV related 3 (1.4) Congenital malformation 10 (4.7) Posterior urethral valves 6 Renal agenesis 4 Renal vein thrombosis 1 (0.5)
    26. 26. 211 Patients with ARF over an 18 year period Dialysis indicated in 108 patients Only 24 had PD– due to resource availability and cost Primary causes of death- uremia, infection, anemia, hypertension and LACK of Dialysis The etiology of acute renal failure- Nigeria ( Anochie & Eke Peds Neph 2005:20 1610-1614)
    27. 27. Unique Situations-HD (+/- CRRT) <ul><li>Conditions when maximal solute clearance is needed with less concern on hemodynamic stability </li></ul><ul><ul><li>Auron and Brophy </li></ul></ul><ul><ul><ul><li>Current opinions in Pediatrics 2010 22: 283-188 </li></ul></ul></ul><ul><ul><li>Quan and Quigley </li></ul></ul><ul><ul><ul><li>Current opinions in Pediatrics 2005 17: 205-209 </li></ul></ul></ul>
    28. 28. Vancomycin clearance High efficiency dialysis membrane Time of therapy Vanc level (mic/dl) Rx Rx Rx Rebound Rebound
    29. 29. Unique Situations-CRRT <ul><li>When hemodynamic instability and highly catabolic conditions are present </li></ul><ul><ul><li>Sepsis </li></ul></ul><ul><ul><li>Bone Marrow Transplantation </li></ul></ul><ul><ul><ul><li>Goldstein SL Seminars in Dialysis 2009; 22; 180-184 </li></ul></ul></ul><ul><ul><ul><li>Walters et al Pediatr Neph 2009 24; 37-38 </li></ul></ul></ul>
    30. 30. Stem Cell Transplant: ppCRRT <ul><li>51 patients in ppCRRT with SCT </li></ul><ul><li>Mean %FO = 12.41 + 3.7%. </li></ul><ul><li>45% survival </li></ul><ul><ul><li>Convection: 17/29 survived (59%) </li></ul></ul><ul><ul><li>Diffusion: 6/22 (27%), p<0.05 </li></ul></ul><ul><li>Survival lower in MODS and ventilated patients </li></ul>Flores FX et al: Pediatr Nephrol. 2008 Apr;23(4):625-30
    31. 31. Intensive vs non Intensive RRT <ul><li>HD and CRRT at 6 days per week and 35 mls/kg/hr daily </li></ul><ul><li>Vs. </li></ul><ul><li>HD and CRRT at 3 days per week and 20 mls/kg/hr daily </li></ul><ul><ul><li>Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury The VA/NIH Acute Renal Failure Trial Network* </li></ul></ul><ul><ul><ul><li>NEJM july 3, 2008 vol. 359 no. 1 </li></ul></ul></ul>
    32. 32. The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20 Enrollment, Randomization, and Follow-up of Study Patients
    33. 33. Intensive vs Conventional
    34. 34. The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20 Primary and Secondary Outcomes
    35. 35. The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20 Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death at 60 Days, According to Baseline Characteristics (Panel B)
    36. 36. The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20 Summary of Complications Associated with Study Therapy
    37. 37. Conclusion of ATN Study <ul><li> Intensive renal support in critically ill patients with AKI did not decrease mortality, improve recovery of kidney function, or reduce the rate of non-renal organ failure as compared with less-intensive therapy involving a defined dose of IHD three times per week and CRRT at 20 ml per kilogram per hour. </li></ul>
    38. 38. Copyright restrictions may apply. Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560 Flow chart of the SHARF 4 study
    39. 39. Copyright restrictions may apply. Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560 Outcome in patients randomized to intermittent (IRRT) or continuous (CRRT) renal replacement therapy
    40. 40. Copyright restrictions may apply. Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560 Survival curves in patients randomized to intermittent (IRRT) or continuous (CRRT) renal replacement therapy investigating ICU mortality and hospital mortality
    41. 41. Cost of Dialysis Equipment (in U.S. dollars) <ul><li>Manual Peritoneal Dialysis </li></ul><ul><li>Device: Dialy-Nate Manual PD set </li></ul><ul><li>Manufacturer: Utah Medical Products </li></ul><ul><li>Cost per Unit: $88.75 (New set Required every 24-72 h) </li></ul><ul><li>Cost of additional Supplies: 1.5% Dineal (Baxter) $24.43/2.0L </li></ul>
    42. 42. Cost of Dialysis Equipment (in U.S. dollars) cont. <ul><li>Manual Peritoneal Dialysis </li></ul><ul><li>Device: Ultra Set (Y-set) </li></ul><ul><li>Manufacturer: Baxter </li></ul><ul><li>Cost per unit: $6.95 (New unit required for each exchange) </li></ul><ul><li>Cost of additional Supplies: 1.5% Dianeal (Baxter) $24.43/2.0L </li></ul>
    43. 43. Cost of Dialysis Equipment (in U.S. dollars) cont. <ul><li>Automated Peritoneal Dialysis </li></ul><ul><li>Device: Freedom Cycler </li></ul><ul><li>Manufacturer: Fresenius </li></ul><ul><li>Cost per unit: $12,295.00 </li></ul><ul><li>Cost of additional supplies: Pediatric Tubing set $32.00 each </li></ul>
    44. 44. Cost of Dialysis Equipment (in U.S. dollars) cont. <ul><li>Intermittent Hemodialysis </li></ul><ul><li>Device: C3 </li></ul><ul><li>Manufacturer: Gambro </li></ul><ul><li>Cost per unit: $18,000.00 </li></ul><ul><li>Cost of additional Supplies: 100HG dialyzer $50.00 each; </li></ul><ul><li>pediatric bloodlines $11.40 each </li></ul>
    45. 45. Cost of Dialysis Equipment (in U.S. dollars) cont. <ul><li>Continuous Hemofiltration </li></ul><ul><li>Device: Prisma </li></ul><ul><li>Manufacturer: Gambro </li></ul><ul><li>Cost per unit: $25,000.00 </li></ul><ul><li>Cost of additional supplies: M60 hemofilter set </li></ul><ul><li>(includes filter and bloodlines) $160.00 </li></ul><ul><li>Normocarb dialysate concentrate </li></ul><ul><li>(Dialysis Solutions) $20.00/3.0L </li></ul>
    46. 46. Conclusion <ul><li>RRT modality comparison shows that the dose of RRT and the choice of RRT may not effect survival </li></ul><ul><li>Indication to begin, end is still of question </li></ul><ul><li>Do what you do well and improve your care of patient with AKI </li></ul>

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