Fluid is a Drug: Late Conservative Fluid Management
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Transcript of Fluid is a Drug: Late Conservative Fluid Management
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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
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Disclosure Summary• Sean M Bagshaw, MD, MSc
– Consultancy: Gambro Inc.– Speaking: Gambro Inc., Alere Inc.
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Learning Objectives
• Review and Discuss:–Fluid Overload
–Fluid Management
–Concept of “De-Resuscitation”
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‘The dose makes the poison’
Paracelus
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Brierley et al CCM 2009
• Identification/diagnosis
• Therapeutic Monitoring– Individualized
• Early/Aggressive Initial Resuscitation– Hemodynamic
stabilization– Shock reversal
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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
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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 survivalPersistent shock (per hour) ~ >2-fold ↓ OR
survival
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Percent Fluid Overload (%FO)
%FO = Σ [FLUID IN – FLUID OUT] [Admission Weight (kg)]
x 100
Goldstein et al Pediatrics 2001
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Arikan et al Ped CCM 2012
74% reached peak %FO <7
days
n=80
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Goldstein et al Pediatrics 2001
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• “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
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Michael et al Pediatr Nephrol 2004
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%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
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Foland et al CCM 2004
15.1
9.3
15.5
9.2
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Gillespie et al Pediatr Nephrol 2004
n=77
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n=116
Goldstein et al KI 2005
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Sutherland et al AJKD 2010
%FO ~ adj-OR 1.03 (95% CI, 1.01-1.05)
n=297
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Akikan et al PCCM 2012
%FO stratified by Oxygen Index in first 5 days of PICU
Median OI 11.5
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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
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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
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Prowle et al NRN 2010
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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
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Brandstrup et al Ann Surg 2003
n=172
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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
0.09Pneumonia (%) 4.3 12.5 0.13Cardiac arrhythmia (%) 0 9.7 0.03
Cardiopulmonary* (%) 7.2 23.6 0.0
07
Tissue Healing (%) 15.9 30.6 0.04
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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 12.1 0.001
ICU-free days (d 1-28) 13.4 11.2 0.00
1RRT (day 60) (%) 10 14 0.06
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Difference in fluid balance
excluding initial
resuscitation
FACTT - Wiedemann et al NEJM 2006
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Valentine et al CCM 2012
n=168
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Valentine et al CCM 2012
n=168
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Maitland et al NEJM 2011
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24 bags ≈ 9000 mg NaCl ≈
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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?
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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:
NCT01416298Available at: http://www.clinicaltrials.gov/ct2/show/NCT01416298?term=NCT01416298&rank=1
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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
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Thank You For Your Attention!
Questions?bagshaw@ualbert
a.ca