Sean M Bagshaw, MD, MSc
Division of Critical Care Medicine
Faculty of Medicine and Dentistry, University of Alberta
1 st International Symposium on AKI in Children
Cincinnati, Ohio
September 28, 2012

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

– Fluid Overload
– Fluid Management
– Concept of “De-Resuscitation”

Paracelus

• Identification/diagnosis
• Therapeutic Monitoring
– Individualized
• Early/Aggressive Initial
Resuscitation
– Hemodynamic stabilization
– Shock reversal
Brierley et al CCM 2009

Fluids
(mL/kg)
Crystalloid
Control
Active
Red Cells
Control
Active
Inotrope
Control
Active
0-6 6-72 0-72
5
28
10
0
80
90
15.7
45.1
43.1
31.4
58.8
68.6
7.8
29.4
22.4
19.6
29.4
49.0
11.8% vs. 39.2%
HR 3.8; 95% CI, 1.6-7.2, p=0.002
Oliveira et al ICM 2008

Outcomes Appropriate Fluid Therapy
(n, %)
All patients (n=91)
Shock Reversed (n=24)
Persistent Shock (n=67)
Survivors (n=65)
41 (45)
24 (100)
17 (25)
32 (49)
Non-Survivors (n=26) 9 (35)
Shock reversal ~ >9-fold ↑ OR survival
Persistent shock (per hour) ~ >2-fold ↓ OR survival
Han et al Pediatrics 2003

%FO = Σ [FLUID IN – FLUID OUT] x 100
[Admission Weight (kg)]
Goldstein et al Pediatrics 2001

n=80
74% reached peak
%FO <7 days
Arikan et al Ped CCM 2012

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

15.1
9.3
15.5
9.2
Foland et al CCM 2004

n=77
Gillespie et al Pediatr Nephrol 2004

n=116
Goldstein et al KI 2005

n=297
%FO ~ adj-OR 1.03
(95% CI, 1.01-1.05)
Sutherland et al AJKD 2010

%FO stratified by Oxygen Index in first 5 days of PICU
Median OI 11.5
Akikan et al PCCM 2012

Late AKI
Early AKI
Any ARF 36% (n=1120)
Mean fluid balance (L/24hr)
Late ARF 25% (n=278)
CRRT 25% (n=278)
No AKI
Payen et al Crit Care 2008

Adj-OR death for fluid overload at
RRT initiation
2.07, 95%CI, 1.27-3.37
Bouchard et al KI 2009

Prowle et al NRN 2010

• 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

n=172
Brandstrup et al Ann Surg 2003

Complication
Pulmonary edema (%)
Pulmonary congestion (%)
Pneumonia (%)
Cardiac arrhythmia (%)
Cardiopulmonary* (%)
Tissue Healing (%)
Conservative
(n=69)
0
2.9
4.3
0
7.2
15.9
Liberal
(n=72)
5.6
11.1
12.5
9.7
23.6
30.6
p
0.20
0.09
0.13
0.03
0.007
0.04
Brandstrup et al Ann Surg 2003

Variable CON LIB p
Death (d 60) (%) 25.5
28.4
0.30
Ventilator-free days (d 1-28)
ICU-free days
(d 1-28)
14.6
13.4
RRT (day 60) (%) 10
12.1
11.2
14
0.001
0.001
0.06
FACTT - Wiedemann et al NEJM 2006

Difference in fluid balance excluding initial resuscitation
FACTT - Wiedemann et al NEJM 2006

n=168
Valentine et al CCM 2012

n=168
Valentine et al CCM 2012

Maitland et al NEJM 2011

24 bags ≈ 9000 mg NaCl ≈

• Body has not evolved a natural mechanism to remove excess ↑ Na+ and water
– When can fluid be ideally removed? Triggers?
– How much fluid should/must be removed?
– What is the timeline for active elimination?

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

• (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

bagshaw@ualberta.ca