Transcript Bagshaw-Fluid-Drug Late - Pediatric Continuous Renal
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 1 st 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) 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
Percent Fluid Overload (%FO)
%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
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
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 Death (d 60) (%) Ventilator-free days (d 1-28) ICU-free days (d 1-28) RRT (day 60) (%) CON 25.5
14.6
13.4
10 LIB 28.4
12.1
11.2
14 p 0.30
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 ≈
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