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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 DO2Adequate DO2

Adequate contractilityAdequate contractility

Optimal actin-myosin matchOptimal actin-myosin match

Normal CVPNormal 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

Decreased RV SV�� RV Preload�� RV Afterload

� LV Preload� LV Preload � LV SV� 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, Vigileo40% MORE fluidLower lactateFewer “complications”

PVI, Masimo1/3 LESS fluidLower 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 ∆SVI/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

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

Metabolic

• Mental status, urine output

• Lactate

• S(c)vO2

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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

Lactate: the data

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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… Metabolic

• Mental status, urine output

• Lactate

• S(c)vO2

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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?

DOGS

Humans w/ sepsis

Humans w/ shock

Changes in SvO2 and ScvO2

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Metabolic goals

• Lactate and ScvO2

– Base deficit?– A-V CO2 gradient?

• Physiological rationale meets objective data.

In summary…

• Supply/demand mismatch

• Detected by straightforward labs

• No target-specific therapies: just get more oxygen to the cells

Putting it all together:

• Volume isn’t easy

• Volume is important

• Common conditions; competing goals• Stepwise plan

– Hemodynamic– Metabolic

The end

The End