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6/1/2013
1
Goal-Directed Fluid Resuscitation
Christopher G. Choukalas, MD, MS Department of Anesthesia and Perioperative Care
University of California, San Francisco
Obligatory joke
• Keep your eye on the food.
The case for why it matters
• Fluid balance a common concern
• Sepsis
• ALI/ARDS
• Sepsis PLUS ARDS!
Sepsis: More is more
• Some impressive fluid totals
Study Control Intervention
Jansen (8 hrs) 2.2L 2.7L
Jones (6 hrs) 4.5L 4.3L
Rivers (6 hrs) 3.5L 5L
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Or is it?
• Retrospective analysis of VASST trial
– 778 pts w/ septic shock on NE
• Divided into quartiles based on total fluid
in at 12 hrs, 4 days
Dry Quartile Wet Quartile
12 hours +0.7L +8.2L
4 days +1.6L +20.5L
Boyd, JH, et al. 2011. CCM. 39(2)
Sepsis + CVP = Death
• Outcomes: Quartile x 28 d mortality
• Early (12 hrs) and Late (4 d) “dry-ness”
saved lives:
– HR 0.57 and 0.47, respectively
Survival Dry Quartile Wet Quartile
12 hours 81% 58%
4 days 83% 65%
Boyd, JH, et al. 2011. CCM. 39(2)
Just the FACTTs
• 1001 w/ ALI randomized to liberal or
conservative fluid algorithms
• Varying amounts of fluid, furosemide,
dobutamine
Outcome Conservative Liberal
Fluid total (day 7; mL) -136 +6990
Vent-Free days
ICU-Free days
Dialysis
CNS failure free days
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Outcome Conservative Liberal
Mortality (60d) 25.5% 28.4% (ns)
Vent-Free days
ICU-Free days
Dialysis
CNS failure free days
Outcome Conservative Liberal
Mortality (60d) 25.5% 28.4% (ns)
Vent-Free days +++
ICU-Free days +++
Dialysis
CNS failure free days
Outcome Conservative Liberal
Mortality (60d) 25.5% 28.4% (ns)
Vent-Free days +++
ICU-Free days +++
Dialysis Less More (ns)
CNS failure free days +++
• Patients with Sepsis who developed ALI
• 4 groups:
– Adequate initial + Conservative late fluids
– Adequate initial only
– Conservative late only
– Neither
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Murphry, CV, et al. 2009. Chest. 136(1)
It matters
• So how do we do it?
I would posit two factors:
• Hemodynamic:
– Is the circulation adequate?
• Metabolic
– Are oxygen delivery and utilization adequate?
• Both have their own goals.
Hemodynamic Goals
• Blood pressure
• CVP
• Dynamic respiratory indices:
– Pulse pressure/systolic pressure/perfusion
index variation
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Hemodynamic Goals
• Blood pressure
• CVP
• Dynamic respiratory indices:
– Pulse pressure/systolic pressure/perfusion
index variation
Blood pressure
• A proxy for flow, end organ perfusion
• Flow = pressure/resistance
• Do we ever really KNOW resistance?
Wax, et al.
• Non-cardiac cases with both ABP and
NIBP.
• Compared SBP, DBP, and MAP btwn
technologies:
– A-line alone vs A-line + cuff
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Randomized trials
Interesting review
• Reviewed 2 trials and 1 meta-analysis (13
studies)
– Target BP
– Actual BP
• Dissociation
– BPs invariably higher than goal
– Higher goal ranges permitted higher actual
ranges: pressors
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Blood pressure
• Necessary but not sufficient
• Goals are nebulous
• Supra-normal levels common, not helpful
Hemodynamic
• Blood pressure
• CVP
• Dynamic respiratory indices:
– Pulse pressure/systolic pressure/perfusion
index variation
Concept: assumptions
Adequate DO2
Adequate contractility
Optimal actin-myosin match
Normal CVP
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The data
• Critical target in EGDT for sepsis
• Incorporated into SSC guidelines
Marik, PE, et al. 2008. Chest. 134(1)
Fluid responsiveness and total
blood volume
• Prong one:
– Volume responsiveness
– Cardiac output before and after fluid
challenge
– 19 evaluated CVP and volume
responsiveness
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Fluid responsiveness
• Calculated a Receiver Operating
Characteristic curve
• Likelihood that at any given point (CVP
level, score, etc) the true positives will
exceed false positives.
• Higher = better discrimination
Volume responsiveness
Marik, PE, et al. 2008. Chest. 134(1)
CVP
• Necessary?
• Certainly not sufficient
• Potentially misleading
Hemodynamic
• Blood pressure
• CVP/wedge
• Dynamic respiratory indices:
– Pulse pressure/systolic pressure/perfusion
index variation
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The Principles
Decreased RV SV
RV Preload
RV Afterload
LV Preload LV SV
Applies to lots of measures
• Systolic pressure variation
• Pulse pressure variation
• Plethysmogram variation
• Outcome is “fluid responsiveness”
Variations on a theme…
• A waveform…
• A peak and trough…
• And a proprietary algorithm:
The data
• Small studies
• Mostly OR
SVV, Vigileo
40% MORE fluid
Lower lactate
Fewer “complications”
PVI, Masimo
1/3 LESS fluid
Lower lactate
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• 29 studies, 685 patients
– 9 ICU
– 20 OR (15 in cardiac surgery)
• All included correlation/ROC between
SPV, PPV, or SVV and ΔSVI/CI after a
fluid challenge.
Measure r AUC for ROC Threshold
PPV 0.78 0.94 12.5%
SVV 0.72 0.84 15.3%
SPV 0.72 0.86
CVP 0.56
ECOM ECOM
• ETT-based electrodes
• Current generated by flow in ascending
aorta
• Current + Nomogram = SV
• SV CO, SVV
• R2 = 0.63
Wallace, AW, et al. Under Review.
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Now, keep in mind…
• Regular HR
• Sedated, mechanically ventilated
• Vt = 8 mL/kg
• Pressors?
PVI + NE = NEB
Monnet, et al Biais, et al
Population 35 ICU patients on NE 35 ICU patients on NE
Gold Standard TD PPV > 13%
SensitivityFR 43 58
SpecificityFR 90 61
AUCROC 0.68 0.69
100
72
0.93
Monnet, et al
Population 35 ICU patients on NE
Gold Standard TD
SensitivityFR 43
SpecificityFR 90
AUCROC 0.68
Hemodynamic goals
• Numerous
• State of the art: Dynamic indices
– PPV
– SPV
– PVI
– VTI and esophageal doppler
• Necessary but not sufficient
Metabolic
• Mental status, urine output
• Lactate
• S(c)vO2
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Metabolic
• Mental status, urine output
• Lactate
• S(c)vO2
Physical exam
• Evidence of end-organ perfusion and
function
• Slow to change
• Numerous confounders
• Summarily dismissed
Metabolic
• Mental status, urine output
• Lactate
• S(c)vO2
Lactate
• The product of anaerobic respiration
• Presence implies inadequate oxygen
utilization, shock
• Easily, quickly measured in arterial blood
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Lactate: the data
Two trials:
• JAMA: 300 patients, EGDT vs lactate
clearance
– Non-inferiority
• AJRCCM: 348 patients, EGDT vs lactate
clearance
– Improved mortality (multivariate)
– Less time on vent, in ICU
How did they do it?
Jones, et al (JAMA) Jansen et al (AJRCCM)
Monitoring interval 2 2
Goal 10% clearance 20% clearance
Fluid totals (L) Control: 4.3
Intervention: 4.5ns
Control: 2.2
Intervention: 2.7*
Outcome Non-inferiority to EGDT Decreased time on vent,
in ICU
The underpinnings…
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Metabolic
• Mental status, urine output
• Lactate
• S(c)vO2
How it’s used:
ScvO2 attributed to:
Supply (cardiac output)
Demand (hypermetabolism)
• In either case, treat by increasing DO2
– Volume, inotropes, RBCs
• But does it work?
ScvO2
• The cornerstone of Early Goal-Directed
Therapy.
• And we know that targeting SvO2
mortality.
– Septic, cardiogenic shock in humans, dogs
– ScvO2 = SvO2?
ScvO2
SvO2
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DOGS
Humans w/ sepsis
Humans w/ shock
Changes in SvO2 and ScvO2
Metabolic goals
• Lactate and ScvO2
– Base deficit?
– A-V (CO2) gradient?
– A-V (CO2)cer gradient?
• Physiological rationale meets objective
data.
Putting it all together:
• Volume isn’t easy
• Volume is important
• Common conditions; competing goals
• Stepwise plan
– Hemodynamic
– Metabolic
The end
The End