fluid sepsis ny_2013a
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Marik's fluid slidesTRANSCRIPT
Fluid in Sepsis: A New ParadigmPaul Marik, MD, FCCP, FCCM
Disclosures
Stocks
Advisory boards
Grants
Speakers Bureau
None
Scientific Disclosures
Three Great Myths in the management of
sepsis
Sepsis is associated with tissue hypoxia
Protocols to “optimize” CI or DO2 improve
outcome
Sepsis is “volume depleted” state
JAMA 1992;267:1503
Ronco JJ, et al. JAMA 1993;270:1724
4ml/kg/min
N Engl J Med 1994; 330:1717
From: Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in
Patients With Septic Shock: A Randomized Clinical Trial
JAMA. 2013;():-. doi:10.1001/jama.2013.278477
0
100
200
300
400
500
600
BL 24 hr 48 hr 72 hr
DO2
Esmolol Control
From: Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in
Patients With Septic Shock: A Randomized Clinical Trial
JAMA. 2013;():-. doi:10.1001/jama.2013.278477
Time Hrs
0 20 40 60 80 100 120
0
100
200
400
500
600
La
cta
te
1.0
1.5
2.0
2.5
3.0
Time vs Lactate - E
Time vs Lactate - C
DO2/VO2
DO2
From: Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in
Patients With Septic Shock: A Randomized Clinical Trial
JAMA. 2013;():-. doi:10.1001/jama.2013.278477
Oxygen kinetics in sepsis
Oxygen requirement are not increased in patients
with sepsis
An oxygen debt does not exist in patients with
sepsis
Lactate is produced aerobically as part of the stress
response
Attempts to increase DO2 in response to an
elevated lactate is
Illogical and devoid of scientific evidence
Likely to be harmful
Historical Perspective
Lancet, Feb 4 1882
His first patient was an elderly women who had reached
the last moments of her earthly existence. “Having no
precedent to guide me I proceeded with much caution”
His first patient was an elderly women who had reached
the last moments of her earthly existence. “Having no
precedent to guide me I proceeded with much caution”
Latta inserted a tube into the basilic vein and injected
ounce after ounce of fluid, closely observing the patient.
His first patient was an elderly women who had reached
the last moments of her earthly existence. “Having no
precedent to guide me I proceeded with much caution”
Latta inserted a tube into the basilic vein and injected
ounce after ounce of fluid, closely observing the patient.
“the sunken eyes and fallen jaw, pale and cold extremities
bearing the manifest imprint of deaths signet, began to
glow with returning animation; the pulse returned to the
wrist”
From this to …. The “Rivers” Protocol
Goals of Hemodynamic Resuscitation
Achieve an adequate perfusion pressure
MAP > 65 mmHg
Improve microcirculatory flow
Limit tissue edema
Crit Care Med 2013; 41:34
The Hemodynamic derangements of sepsis
Vasoplegic shock/vasodilatory shock
Nitric oxide
ANP
KATP
Vasopressin
Leaky capillaries
Glycocalyx
Endothelial junctions
Myocardial depression
Nitric Oxide
1. NO/ANP
2. Activation of KATP
3. Vasopressin deficiency
VGEF
Angiopoeitin 2
Starling Principle
Starling (1896) states fluid exchange is governed by
high vascular COP and low interstitial COP
Recently it is proved that intravascular COP is
almost identical to extravascular one
Jacob M. et al Cardiovascular Research 2007; 73:
575-586
EG consists of membrane-bound proteoglycans and glycoproteins network in which plasma or endothelial proteins are retained - forms the endothelial surface layer (ESL)
ESL thickness is 1μm
Jacob M. et al Cardiovascular Research 2007; 73:
575-586
Endothelial Glycocalyx
The Glycocalyx Denuded in Sepsis
Crit Care Med 2008; 36:1701
Norepi 0.8 ug/kg/min Norepi 0.4 ug/kg/min
Dobutamine 5 ug/kg/minLVFAC= left ventricular fractional area contraction
The Hemodynamic derangements of sepsis
FLUIDS INCREASE Vasoplegic shock/vasodilatory shock
Nitric oxide
BNP
KATP
Vasopressin
FLUIDS INCREASE Leaky capillaries
Glycocalyx
Endothelial junctions
FLUIDS INCREASE Myocardial depression
Nitric Oxide
Myocardial edema
Fluid may not be the most efficient method to increase
MAP in septic shock
Crit Care Med 2007;35:477
% change in cardiac Index
Eur J Pharmacology 2009;621:67
BNP damages glycocalyx
Inc atrial pressure leads to a release of natriuretic
peptides
ANP/BNP shed off the glycocalyx components
(syndecan -1) into the circulation
This is accompanied by significant rapid shifts of
intravascular fluid into interstitial space
Bruegger D. et al Am J Physiol 2005; 289: H1993
Ueda S, et al. Shock 2006;26:123
Resuscitated according to EGDRx
0
200
400
600
800
1000
1200
1400
Admission Day 1 Day 2 Day 4
Survivors Non-survivors
BNP (pg/ml)
Bark BP, et al. Crit Care Med 2013;41
CLP
Excess fluid Increases mortality in
patients with sepsis
The Evidence: Experimental Models
Crit Care 2009; 13:R186
48 pigs randomized to endotoxin infusion, fecal peritonitis
or control
Each group randomized to Moderate (10ml/kg/hr) or High
volume-EGDRx (20 ml/kg/hr) LR resuscitation for 24 hrs
High Volume-EGDRx Group
Higher CI
Higher MAP
Higher PCWP
Lower lactate
Higher SmvO2
Crit Care 2009; 13:R186
The Evidence: Clinical Studies
Alsous F et al. Chest 2000;117:1749
The Soap Study
Crit Care Med 2006; 34:344
Crit Care Med 2011;39:256-265
Crit Care Med 2011;39:256-265
Optimal survival occurred with a
positive fluid balance of approximately
3 liters at 12 hours
Patients with CVP <8
mmHg at 12 hrs had
the lowest mortality.
Crit Care Med 2011;39:256-265
Days
Association of cumulative fluid balance on outcome
in ALI: A review of the ARDSnet cohort
J Intens Care Med 2009;24:35
2009; 136:102-109
Non-survivors
Survivors
Resp Med 2008;102:956
Mortality 48 hrs Mortality 4 weeks
Maitland K, et al. NEJM 2011; 364:2483
Fluid resuscitation in sepsis
“Give them as much as they need and
not a drop more”….
Where's the Blood Volume?
Crit Care Med 2012;40:3146
Before After
Dose norepinephrine
(ug/kg/min)0.3 0.19
CI (l/min/M2) 3.47 3.28
CI change by PLR (%) 1 8
Mean systemic pressure
(mmHg)33 26
GEDVI (ml/m2) 819 774
The lowest mortality was seen in patients with lower SOFA scores
and early norepinephrine administration after admission.
Conclusion: Both the time of starting norepinephrine after
admission to the
ICU and the degree of organ dysfunction have an important bearing
on subsequent
Outcome
Crit Care Med 2000;28:947
Geleon A, et al. Crit Care Med 2014 (ePub
Normal adrenal function
Impaired adrenal function
Before HC After HC
Annane, British Journal of Clinical Pharmacology, 1998
Effect of Hydrocortisone on Sepsis-Induced
Hypotension
SV
EVLW
Preload
Large increase in EVLW
Small increase in CO
The Frank-Starling & Marik-Phillips Curves
Large increase in CO
Small increase in EVLW
Sepsis
Techniques to Assess Fluid Responsiveness
Excellent
Fair-Good
Worthless
ROC Curves & Diagnostic Accuracy
Assessment of fluid
responsivenessTechnique
CVP/PAOP
IVC/SVC diameter
FTc (LVETc)
RVEDV/LVEDA/GEDI
IVC/SVC - respiratory variation
PPV/SVV/PVI
Aortic blood flow - respiratory
variation
Passive Leg Raising
(PLR)
Technology
CVP/PAC
Non calibrated pulse contour
Bioimpedance
Ultrasound (IVC/SVC)
Ultrasound (IVC/SVC resp. variability)
Pleth waveform (PVI)
ECHO- Aortic Doppler (resp. variability)
Calibrated pulse contour (PPV/SVV)
Esophageal Doppler (PLR &
volume)
Calibrated pulse contour (PLR &
volume)
Assessment of fluid responsiveness
Technique
PLR
Volume
Challenge
Technology
Esophageal Doppler
Calibrated pulse
contour
NICOM -
Bioreactance
Study name sample size AUC
Monnet CCM 2006 71 0.96
Lafanéchère CC 2006 22 0.95
Lamia ICM 2007 24 0.96
Maizel ICM 2007 34 0.89
Monnet CCM 2009 34 0.94
Thiel CC 2009 102 0.89
Biais CC 2009 30 0.96
Preau CCM 2010 34 0.94
351 0.95
Study name sample size AUC
Monnet CCM 2006 71 0.75
Monnet CCM 2009 34 0.68
Preau CCM 2010 34 0.86
139 0.76
PLR-induced changes in PP
Which Fluid?
Crystalloids
Balanced Salt Solutions (BSS)
Ringers
Plasmalyte
Un-physiologic Salt Solutions
(USS)
NaCl
Colloids
Albumin (USS)
Starches (USS)
Chloride liberal vs. Chloride Restrictive
Strategy
Anesth Analg 2013:117:412
“Ab-Normal” Saline vs. Balanced Salt
Solution Metabolic and dilutional acidosis
Decreased renal blood flow
Coagulopathy- more bleeding
Increased inflammation
Increased risk of renal failure
Increased risk of death
NEJM 2008;358:125
5% Albumin
Maintains endothelial glycocalyx and “endothelial
function”
Anti-oxidant properties
Anti-inflammatory properties
May limit “third” space loss
Albumin has a number of features that may be theoretically advantageous
in patients with sepsis and SIRS including:
Kozar R, et al. Anesth Analg
2011;112:1289
Pts. with severe sepsis or septic shock (6-24 hr)
Albumin Crystalloid
s
crystalloids
Albumin:
[300 ml at 20% in 3* hrs]
+
crystalloids
Study design
Randomization
Volume replacement
Study design
from day 1 to day 28
Plasma albumin
level
< 30 g/L
≥ 25 g/L≥ 30 g/L
No infusion
of Albumin
Infusion of
Albumin:
200 ml at 20%
in 3* hrs
< 25 g/L
Infusion of
Albumin:
300 ml at 20%
in 3* hrs
Albumin
Marik PE. Chest 2014 (in press)