1. Effect of Timing of Initiation on Short-term Mortality in Critically Ill Children requiring CRRT Modini Vinai, MD Marita Thompson, MD Diane Gollhofer, RN Raymond Quigley, MD

2. Pediatric CRRT CRRT use in critically ill children is increasing Changing spectrum of AKI etiology and incidence Development of pediatric friendly technology Increasing experience and willingness to use CRRT High mortality in children requiring CRRT

3. Potential Factors affecting Survival Systemic Factors Primary Diagnosis Underlying Co-morbidities Severity of Organ Dysfunction Kidney-related Factors Etiology of Renal Injury Severity of Renal Injury Severity of Renal Dysfunction ICU Therapies and Management CRRT-related Factors Timing of Initiation Modality Dose Duration of Therapy SURVIVAL

4. Fluid Overload and Survival – ppCRRT Results Am J Kidney Dis; Vol 55, No 2 (February), 2010: pp 316-325

5. Objectives To evaluate the effect of Timing of Initiation, measured as time from admission to PICU to initiation of CRRT, on short- term mortality of critically ill children requiring CRRT To assess Timing of Initiation as an independent predictor of death

6. Study Design Nested Case-Control Design Inclusion Criteria All patients admitted to the ICUs at CMCD Have undergone CRRT between Jan 1, 2000 and Jan 31, 2009 Exclusion Criteria ECMO support anytime during the CRRT-related ICU admission

7. Statistical Analysis Univariate Analysis Comparing Timing of Initiation between survivors and non- survivors Comparing covariates between survivors and non-survivors Age, Gender, Weight Paediatric Index of Mortality (PIM) II score Fluid Overload Renal Function Presence of Shock States Indication for CRRT Reason for ICU Admission Primary Underlying Diagnosis

8. Statistical Analysis Survival Analysis for different cut-offs of Timing of Initiation Multivariate Logistic Regression Analysis To evaluate if Timing of Initiation is an independent predictor of death

9. Results Total Number of CRRT N = 329 Non-ECMO N = 224 Male: 102 Female: 122 Survivors N = 121 ECMO N = 105 Non-Survivors N = 103

10. Survivors Vs. Non-Survivors VariableSurvivors (N=121) Mean + SEM Non-Survivors (N=103) Mean + SEM Age (in Months) 110.6 + 7.2105.0 + 8.0 Weight (in Kg) 38.0 + 2.735.4 + 2.8 GenderM : F = 57 : 64M : F = 45 : 58 Paediatric Index of Mortality II Score 10.4 + 1.2 15.7 + 1.7 * Presence of Shock States66% 81% * * p-value < 0.05

11. Primary Underlying Diagnosis * * * * Number of Patients Primary Underlying Diagnosis * p-value < 0.05

12. Indication for CRRT * Number of Patients Primary Indication for CRRT * p-value < 0.05

13. Fluid Overload and Renal Function * p-value < 0.05 VariableSurvivors (N=121) Mean + SEM Non-Survivors (N=103) Mean + SEM % Fluid Overload10.5 + 1.3 17.6 + 1.5 * Hourly UO at Admission (ml/Kg/Hr) 1.5 + 0.12.0 + 0.2 Hourly UO at Initiation (ml/Kg/Hr) 1.4 + 0.11.3 + 0.1 eGFR at Admission (ml/min/1.73m2) 59.6 + 4.5 73.6 + 5.1 * eGFR at Initiation (ml/min/1.73m2) 39.7 + 3.438.4 + 2.7 % eGFR 21.2 + 3.0 31.8 + 4.8 *

14. Timing of Initiation Timing of Initiation in Days Patients 40 20 0 20 40 60 80 100

15. Timing of Initiation (in Days) Survivors Vs. Non-Survivors Wilcoxon Rank Score Median for Survivors 1.23 Days Vs. Median for Non-Survivors 2.86 Days *

16. Kaplan-Meier Curves Timing of Initiation 3 days Logrank Statistic 4.27 (p=0.0389) < 3 Days > 3 Days

17. Timing of Initiation as an Independent Predictor CovariateUnadjusted OR (95% CI)Adjusted OR (95% CI) Timing of Initiation1.065 (1.012, 1.118)1.129 (1.037, 1.228) PIM II Score1.025 (1.005, 1.044)1.021 (1.000, 1.043) Fluid Overload0.999 (0.994, 1.004)1.074 (1.038, 1.110) Presence of Shock States2.127 (1.148, 3.939)NS Underlying DiagnosisNS

18. Summary Survivors had earlier Timing of Initiation of CRRT compared to Non-Survivors. A 6.5% increase in mortality is noted for every day of delay in initiating CRRT (unadjusted mortality OR = 1.065). The Timing of Initiation was an independent predictor in our final logistic regression model (p-value = 0.0049).

19. Limitations of our Study Retrospective Study Design Accuracy of Fluid Overload measurements PIM II Scores Questionable accuracy of measurement Likely underestimates the risk of mortality in children with AKI eGFR is a poor indicator of renal function in AKI Single Center Study

20. Conclusions The Timing of Initiation of CRRT is an independent predictor of mortality in critically ill children requiring CRRT. Hence, early identification of the need for CRRT in critically ill children is essential.