Sean M Bagshaw, MD, MScDivision of Critical Care Medicine

Faculty of Medicine and Dentistry, University of Alberta

1st International Symposium on AKI in Children

Cincinnati, OhioSeptember 28, 2012

Fluid is a Drug: Late

Conservative Fluid

Management

Disclosure Summary

• Sean M Bagshaw, MD, MSc– Consultancy: Gambro Inc.– Speaking: Gambro Inc., Alere Inc.

Learning Objectives

• Review and Discuss:

–Fluid Overload

–Fluid Management

–Concept of “De-Resuscitation”

‘The dose makes the poison’

Paracelus

Brierley et al CCM 2009

• Identification/diagnosis

• Therapeutic Monitoring– Individualized

• Early/Aggressive Initial Resuscitation– Hemodynamic

stabilization– Shock reversal

11.8% vs. 39.2%HR 3.8; 95% CI, 1.6-7.2,

p=0.002Oliveira et al ICM 2008

Fluids (mL/kg)

0-6 6-72 0-72

Crystalloid Control Active

528

100

8090

Red Cells Control Active

15.745.1

43.131.4

58.868.6

Inotrope Control Active

7.829.4

22.419.6

29.449.0

Han et al Pediatrics 2003

Outcomes Appropriate Fluid Therapy(n, %)

All patients (n=91) 41 (45)

Shock Reversed (n=24)

24 (100)

Persistent Shock (n=67)

17 (25)

Survivors (n=65) 32 (49)

Non-Survivors (n=26)

9 (35)

Shock reversal ~ >9-fold ↑ OR survival

Persistent shock (per hour) ~ >2-fold ↓ OR survival

Percent Fluid Overload (%FO)

%FO = Σ [FLUID IN – FLUID OUT] [Admission Weight (kg)]

x 100

Goldstein et al Pediatrics 2001

Arikan et al Ped CCM 2012

74% reached peak %FO <7

days

n=80

Goldstein et al Pediatrics 2001

• “It is possible that in some cases CVVH/D may be a prevention, rather than a treatment, for worsening degrees of fluid

overload.”

• “Early initiation of CVVH to allow for sufficient blood product and nutrition administration, while preventing fluid overload may

improve patient survival…”Goldstein et al Pediatrics 2001

Michael et al Pediatr Nephrol 2004

%FO>10% for PICU Admission: 68.4% vs. 22.1%, p<0.001

Risk factors for %FO>10% ~ smaller children; AKI

Indications for CRRT Initiation ~ FO in 39%

%FO at CRRT Initiation ~ 10.6% vs. 13.9% (p=NS)

Benoit et al Pediatr Nephrol 2007; Flores et al Pediatr Nephrol 2008

Foland et al CCM 2004

15.1

9.3

15.5

9.2

Gillespie et al Pediatr Nephrol 2004

n=77

n=116

Goldstein et al KI 2005

Sutherland et al AJKD 2010

%FO ~ adj-OR 1.03 (95% CI, 1.01-1.05)

n=297

Akikan et al PCCM 2012

%FO stratified by Oxygen Index in first 5 days of PICU

Median OI 11.5

Payen et al Crit Care 2008

Any ARF 36% (n=1120)

Early ARF 75% (n=842)

Late ARF 25% (n=278)

CRRT 25% (n=278)

Early AKI

Late AKI

No AKI

Mean fluid balance (L/24hr) HR 1.21, 95%CI, 1.13-1.28,

p<0.001

Fluid Overload at RRT Initiation

Bouchard et al KI 2009

Adj-OR death for fluid overload at RRT initiation

2.07, 95%CI, 1.27-3.37

Prowle et al NRN 2010

Challenges…

• Available literature:– Small sample size– Retrospective or Registry data

• Few data from INTERVENTIONAL trials:– Focused specifically on children!– Fluid management AFTER initial

resuscitation– Focused on strategies for fluid

management:• Volume: “Conservative” vs. “Liberal”

(standard)• Type: Crystalloid or Colloid; Isotonic or

Balanced

Brandstrup et al Ann Surg 2003

n=172

Brandstrup et al Ann Surg 2003

ComplicationConservat

ive(n=69)

Liberal(n=72)

p

Pulmonary edema (%)

0 5.6 0.20

Pulmonary congestion (%)

2.9 11.1

0.09

Pneumonia (%) 4.3 12.5 0.13

Cardiac arrhythmia (%)

0 9.7 0.03

Cardiopulmonary* (%)

7.2 23.60.007

Tissue Healing (%) 15.9 30.60.04

FACTT - Wiedemann et al NEJM 2006

Variable CON LIB p

Death (d 60) (%)

25.5 28.4 0.30

Ventilator-free days (d 1-28)

14.6 12.10.00

1

ICU-free days (d 1-28)

13.4 11.20.00

1

RRT (day 60) (%)

10 14 0.06

Difference in fluid balance

excluding initial

resuscitation

FACTT - Wiedemann et al NEJM 2006

Valentine et al CCM 2012

n=168

Valentine et al CCM 2012

n=168

Maitland et al NEJM 2011

24 bags ≈ 9000 mg NaCl ≈

Next Steps…

• Body has not evolved a natural mechanism to remove excess ↑ Na+ and water

• “De-resuscitation” in MODS/AKI?

– When can fluid be ideally removed? Triggers?

– How much fluid should/must be removed?

– What is the timeline for active elimination?

NGAL-Directed RRT Initiation

Use of Neutrophil Gelatinase-Associated Lipocalin (NGAL)

to Optimize Fluid Dosing, Continuous Renal

Replacement Therapy (CRRT) Initiation and

Discontinuation in Critically Ill Children With Acute

Kidney Injury (AKI)

ClinicalTrials.gov Identifier: NCT01416298

Available at: http://www.clinicaltrials.gov/ct2/show/NCT01416298?term=NCT01416298&rank=1

Summary

• (Excessive) fluid accumulation is bad

• Contribute to and/or worsen AKI/MODS

• Short/longer term injury to non-renal organs

• ↑ Risk morbidity/poor outcomes• Need to better understand ideal

strategies to (safely) mitigate and/or remove excess extravascular fluid

Thank You For Your Attention!

Questions?bagshaw@ualbert

a.ca