Effect of Timing of Initiation on Short-term Mortality in Critically

Ill Children requiring CRRTModini Vinai, MD

Marita Thompson, MDDiane Gollhofer, RN

Raymond Quigley, MD

Pediatric CRRT

CRRT use in critically ill children is increasingChanging spectrum of AKI etiology and incidenceDevelopment of pediatric friendly technology Increasing experience and willingness to use CRRT

High mortality in children requiring CRRT

Potential Factors affecting Survival

Systemic FactorsPrimary Diagnosis

Underlying Co-morbiditiesSeverity of Organ Dysfunction

Kidney-related FactorsEtiology of Renal InjurySeverity of Renal Injury

Severity of Renal Dysfunction

ICU Therapies and Management

CRRT-related FactorsTiming of Initiation

ModalityDose

Duration of Therapy

SURVIVAL

Fluid Overload and Survival – ppCRRT Results

Am J Kidney Dis; Vol 55, No 2 (February), 2010: pp 316-325

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

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

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

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

Results

Total Number of CRRTN = 329

Non-ECMON = 224

Male: 102 Female: 122

SurvivorsN = 121

ECMON = 105

Non-SurvivorsN = 103

Survivors Vs. Non-Survivors

Variable Survivors (N=121)Mean + SEM

Non-Survivors (N=103)Mean + SEM

Age(in Months)

110.6 + 7.2 105.0 + 8.0

Weight(in Kg)

38.0 + 2.7 35.4 + 2.8

Gender M : F = 57 : 64 M : F = 45 : 58

Paediatric Index of Mortality II Score

10.4 + 1.215.7 + 1.7*

Presence of Shock States 66%81%*

* p-value < 0.05

Primary Underlying Diagnosis

** *

*

Num

ber

of P

atie

nts

Primary Underlying Diagnosis * p-value < 0.05

Indication for CRRT

*

Num

ber

of P

atie

nts

Primary Indication for CRRT * p-value < 0.05

Fluid Overload and Renal Function

* p-value < 0.05

Variable Survivors (N=121)Mean + SEM

Non-Survivors (N=103)Mean + SEM

% Fluid Overload 10.5 + 1.317.6 + 1.5*

Hourly UO at Admission (ml/Kg/Hr)

1.5 + 0.1 2.0 + 0.2

Hourly UO at Initiation (ml/Kg/Hr)

1.4 + 0.1 1.3 + 0.1

eGFR at Admission(ml/min/1.73m2)

59.6 + 4.573.6 + 5.1*

eGFR at Initiation(ml/min/1.73m2)

39.7 + 3.4 38.4 + 2.7

% eGFR 21.2 + 3.031.8 + 4.8*

Timing of Initiation

Timing of Initiation in Days

Patie

nts

40 20 0 20 40 60 80 100

Timing of Initiation (in Days)Survivors Vs. Non-Survivors

Wilc

oxo

n R

an

k S

core

Median for Survivors 1.23 Days Vs. Median for Non-Survivors 2.86 Days

*

Kaplan-Meier CurvesTiming of Initiation < 3 days Vs. > 3 days

Logrank Statistic 4.27 (p=0.0389)

< 3 Days

> 3 Days

Timing of Initiation as an Independent Predictor

Covariate Unadjusted OR (95% CI) Adjusted OR (95% CI)

Timing of Initiation 1.065 (1.012, 1.118) 1.129 (1.037, 1.228)

PIM II Score 1.025 (1.005, 1.044) 1.021 (1.000, 1.043)

Fluid Overload 0.999 (0.994, 1.004) 1.074 (1.038, 1.110)

Presence of Shock States 2.127 (1.148, 3.939) NS

Underlying Diagnosis NS NS

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).

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

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.