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5/19/2014 1 Goal-Directed Fluid Resuscitation

Christopher G. Choukalas, MD, MS

Department of Anesthesia and Perioperative Care University of California, San Francisco

Disclosure

• OBS Medical funds a small amount of

research not related to this talk

Obligatory joke

• Not much new this year
• Horse with colic

5/19/2014 2

The case for why it matters

• Fluid balance a common concern
• Sepsis
• ALI/ARDS
• Sepsis PLUS ARDS!
• Patients with Sepsis who developed ALI
• 4 groups:

– Adequate initial + Conservative late fluids – Adequate initial only – Conservative late only – Neither

Murphry, CV, et al. 2009. Chest. 136(1)

5/19/2014 3

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

5/19/2014 4

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?

5/19/2014 5

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

Randomized trials

• This used to be the 2nd joke of the talk

5/19/2014 6

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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The NEJM study

• Randomized to MAP 65 vs 85 (800 total)
• Norepinephrine
• Mortality
• AKI/RRT, stratified by HTN

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

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Concept: assumptions

Adequate DO2 Adequate DO2 Adequate contractility Adequate contractility Optimal actin-myosin match Optimal actin-myosin match Normal CVP Normal CVP

The data

• Critical target in EGDT for sepsis
• Incorporated into SSC guidelines

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Sepsis +  CVP = Death

• 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) Marik, PE, et al. 2008. Chest. 134(1)

5/19/2014 10

Fluid responsiveness and total blood volume

• Volume responsiveness
• Cardiac output before and after fluid

challenge

• 19 evaluated CVP and volume

responsiveness

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)

5/19/2014 11

Deja vu

• 43 studies, half ICU
• Same design

– AUC btwn CVP and ∆SV

• Same pooled AUC

– 0.56

• Same aggressive conclusion

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:

5/19/2014 13

The data

• Small studies
• Mostly OR

SVV, Vigileo 40% MORE fluid Lower lactate Fewer “complications” PVI, Masimo 1/3 LESS fluid Lower lactate

• 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

5/19/2014 14

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.

Now, keep in mind…

• Regular HR
• Sedated, mechanically ventilated
• Vt = 8 mL/kg
• Pressors?

5/19/2014 15

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

5/19/2014 16

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

5/19/2014 17

Lactate

• The product of anaerobic respiration
• Presence implies inadequate oxygen

utilization, shock

• Easily, quickly measured in arterial blood

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

5/19/2014 18

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

5/19/2014 19

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

5/19/2014 20

DOGS

Humans w/ sepsis Humans w/ shock Changes in SvO2 and ScvO2

But does it work?

• Conflicting data

A-V(CO2)

• To the obscure…

5/19/2014 21

The premise:

• Pts admitted to ICU w/ sepsis frequently

have NL ScvO2

• Many

– Still have evidence of hypoperfusion – Still die

EGDT EGDT ScvO2 > 70 ScvO2 > 70 Lactate NL Lactate NL Lactate High Lactate High A-V(CO2) < 6 A-V(CO2) < 6 A-V(CO2) >6 A-V(CO2) >6 ScvO2 < 70 ScvO2 < 70

• 50 such patients

– 26 Low gap – 24 High gap

• The same on many measures:

– SOFA, APACHE II, pressor use

• Over 24 hrs, High gap exhibited

hypoperfusion:

– Persistent lactate – Higher SOFA

5/19/2014 22

• Higher mortality

– 34% – 54% (ns)

• No specific therapy for gap
• Authors recommend augmenting CO

Metabolic goals

• Lactate and ScvO2

– Base deficit? – A-V (CO2) gradient? – A-V (CO2)cer gradient?

• Physiological rationale meets objective

data.

Does any of this…

• Save lives?
• Save money?
• Actually work?

5/19/2014 23

Subgroup Mortality Complications Jadad high

• +++

Jadad low +++ +++ 1980s-1990s +++ +++ 2000s

• +++

5/19/2014 24

5/19/2014 25

• Randomized CT surgery patients to

– CVP and MAP – SVV, EDV index (PiCCO), EVLW

Counted up outcomes

• Less norepinephrine
• Higher CI, ScvO2
• Fewer post-op complications
• Left the ICU and hospital a full day sooner
• No difference in fluid totals, RBCs, UOP

– Timing of fluid: More in the OR.

A great review…

• Alphabet soup

– SVV, PPV, SPV, PVI – LidCO, PiCCO, esCCO, ProAQT

• Some require external calibration
• Some require specific catheters in specific

locations.

5/19/2014 26

Device Calibration Technology Catheter Edwards FloTrac Pulse pressure Standard a- line, proprietary transducer Pulsion PulsioFlex Nomogram or external Pulse Pressure Standard a- line LidCO Nomogram or Li Dilution Pulse pressure or Li dilution Proprietary a- line with Li electrode Pulsion PiCCO None Thermo- dilution Central venous AND central arterial lines

Putting it all together:

• Volume isn’t easy
• Volume is important
• Common conditions; competing goals
• Stepwise plan

– Hemodynamic – Metabolic

• It seems to work

The end

The End