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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