Effect of Timing of Initiation on Short-term Mortality in Critically Ill Children requiring CRRT

1. Effect of Timing of Initiation on Short-term Mortality in Critically Ill Children requiring CRRT ModiniVinai, 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 ICU Therapies and Management SURVIVAL Kidney-related Factors Etiology of Renal Injury Severity of Renal Injury Severity of Renal Dysfunction CRRT-related Factors Timing of Initiation Modality Dose Duration of Therapy

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 Initiationas 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 Initiationbetween 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 ECMO N = 105 Survivors N = 121 Non-Survivors N = 103

10. Survivors Vs. Non-Survivors *p-value < 0.05

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

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

13. Fluid Overload and Renal Function *p-value < 0.05

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

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

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

17. Timing of Initiation as an Independent Predictor

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 Initiationwas 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 • TheTiming 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.