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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.
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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
11.8% vs. 39.2% HR 3.8; 95% CI, 1.6-7.2, p=0.002 Oliveira et al ICM 2008
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] [Admission Weight (kg)] x 100 Goldstein et al Pediatrics 2001
74% reached peak %FO <7 days n=80 Arikan et al Ped CCM 2012
“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
%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) Early ARF 75% (n=842) Late ARF 25% (n=278) CRRT 25% (n=278) Mean fluid balance (L/24hr) HR 1.21, 95%CI, 1.13-1.28, p<0.001 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
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
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
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@ualberta.ca