Bagshaw-Fluid-Drug Late - Pediatric Continuous Renal

Report
Fluid is a Drug:
Late Conservative
Fluid Management
Sean M Bagshaw, MD, MSc
Division of Critical Care Medicine
Faculty of Medicine and Dentistry, University of Alberta
1st International Symposium on AKI in Children
Cincinnati, Ohio
September 28, 2012
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
• Identification/diagnosis
• Therapeutic Monitoring
– Individualized
• Early/Aggressive Initial
Resuscitation
– Hemodynamic
stabilization
– Shock reversal
Brierley et al CCM 2009
Fluids
(mL/kg)
0-6
6-72
0-72
Crystalloid
Control
Active
5
28
10
0
80
90
Red Cells
Control
Active
15.7
45.1
43.1
31.4
58.8
68.6
Inotrope
Control
Active
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
All patients (n=91)
Shock Reversed (n=24)
Persistent Shock (n=67)
Survivors (n=65)
Non-Survivors (n=26)
Appropriate Fluid Therapy
(n, %)
41 (45)
24 (100)
17 (25)
32 (49)
9 (35)
Shock reversal ~ >9-fold ↑ OR survival
Persistent shock (per hour) ~ >2-fold ↓ OR survival
Han et al Pediatrics 2003
Percent Fluid Overload (%FO)
%FO = Σ [FLUID IN – FLUID OUT]
x 100
[Admission Weight (kg)]
Goldstein et al Pediatrics 2001
74% reached peak
%FO <7 days
n=80
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
15.5
15.1
9.3
9.2
Foland et al CCM 2004
n=77
Gillespie et al Pediatr Nephrol 2004
n=116
Goldstein et al KI 2005
%FO ~ adj-OR 1.03
(95% CI, 1.01-1.05)
n=297
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)
EarlyHR
ARF1.21,
75% (n=842)
95%CI, 1.13-1.28, p<0.001
Late ARF 25% (n=278)
CRRT 25% (n=278)
No AKI
Payen et al Crit Care 2008
Fluid Overload at RRT Initiation
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
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
n=172
Brandstrup et al Ann Surg 2003
Conservative
(n=69)
Liberal
(n=72)
p
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
23.6
0.007
Tissue Healing (%)
15.9
30.6
0.04
Complication
Pulmonary edema (%)
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)
14.6
12.1
0.001
ICU-free days
(d 1-28)
13.4
11.2
0.001
10
14
0.06
RRT (day 60) (%)
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 ≈
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 GelatinaseAssociated 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?
[email protected]

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