Goal-Directed Therapy in
Septic Shock
What Goals Matter, What Don’t,
and Why We Should Care
William Owens, MD
Division of Pulmonary and Critical Care Medicine
University of South Carolina
Disclosures
I have no ties, financial or otherwise, with any companies or
products discussed today.
I do have biases, prejudices, and opinions completely
unfounded in fact, which I am always happy to share!
Patients enrolled who had either:
 SBP < 90 after a 20 mL/kg fluid bolus, or
 Lactate > 4 mmol/L
46% vs 30%
INTERVENTION ARM
Early
Antibiotics
Fluid
Resuscitation
Good Genetics
CVP 8-12
Hemoglobin
10 g/dL
ScvO2 ≥ 70%
GOAL: Fill The Tank!
Pulmonary Artery
Catheter
Central Venous
Pressure
AUC 0.56
Measurement
CVP< 8
CVP< 12
CVP< 5
PAOP< 11
PAOP< 11 + CVP< 8
CVP< 8 + SVI< 30
PAOP< 12 + SVI< 30
PPV
51%
47%
47%
54%
54%
61%
69%
NPV
65%
67%
58%
74%
63%
39%
58%
(PPmax – PPmin)
(PPmax + PPmin/2)
PPV≥13% correlates with
preload responsiveness
(AUC 0.91)
* Tidal Volume should be 8 cc/kg
* Breathing should be controlled
and passive
* Cardiac rhythm must be regular
12% change corresponds with fluid responsiveness
PPV 93% NPV 92%
Feissel M, Michard F, Faller J, Teboul J
The respiratory variation in inferior vena cava diameter as a guide to fluid therapy
Intensive Care Med (2004) 30: 1834-1837
LVEDA < 10 cm2 or LVEDA/BSA < 5.5 cm2/m2
corresponds with preload responsiveness
GOAL: Fill The Tank!
CVP is not accurate at
any level
The PA catheter isn’t
much better
Ultrasound and PPV
show promise
Clinical Correlation Is
Required!
GOAL: Hemoglobin ≥ 10 g/dL
CaO2 = 1.34 × Hgb × SaO2
DO2 = CO × CaO2 × 10




838 patients randomized
Transfusion triggers of 7.0-9.0
g/dL versus 10.0-12.0 g/dL
No difference in mortality
overall
Shock
Drop in Hgb > 3 g/dL
NoCoronary
differenceIschemia
in mortality in
patients with coronary artery
disease
Not Applicable to Initial Resuscitation?
Inadequate
Oxygen
Delivery
Benefits
Outweigh
Risks
Transfusion
Increases
DO2 and VO2
Cells Can Use
Delivered
Oxygen
Inadequate
Oxygen Delivery
Healthy humans can
tolerate hemodilution
to 5 g/dL
DO2crit in animals seems to be 3-3.5 g/dL
Microcirculatory hematocrit is relatively
constant at 12-15%
No necrosis at autopsy
Transfusion
Increases DO2
and VO2
Mathematical Coupling
Stored Blood Holds On To Oxygen
Supply Dependency Doesn’t Exist In
Septic Shock
Cells Can Use
Delivered
Oxygen
RBCs are depleted of 2-3
DPG until 24 hours after
transfusion
Free Hemoglobin scavenges NO—
inflammation, vasoconstriction, thrombosis,
oxidative stress
Increasing blood viscosity causes vasodilation via
endothelium-released NO
(much of the benefit of transfusion may be independent of CaO2)
Marik showed that patients transfused stored blood
had consistently lower gastric mucosal pH
(JAMA 1993;269(23):3024– 9)
80%
95%
GOAL: Hemoglobin ≥ 10 g/dL
No evidence for arbitrary
transfusion trigger
Transfused RBCs may worsen
microcirculatory perfusion
Base decision to transfuse on
signs of inadequate oxygen
delivery
•
•
•
•
Rising lactate
Elevated troponin
Ischemic ECG findings
Poor perfusion (i.e., the cold
big toe)
GOAL: Keep ScvO2 ≥ 70%
VO2 = CO × 1.34 × Hgb × [SaO2 –SvO2]
Shoemaker (Chest, 1988)
• Get CI over 4.5 L/min/m2
• DO2I >600 mL/min/m2
• VO2I >170 mL/min/m2
Tuchschmidt (Chest, 1992)
• Supranormal DO2 in Septic Shock
• No Survival Benefit
Gattinoni (NEJM, 1995)
• CI >4.5 L/min/m2
• SvO2 >70%
• No Survival Benefit
• Many patients couldn’t reach physiologic targets
Nguyen et al: ED Resuscitation Improves Survival
(Acad Emerg Med, 2000)
PRO
• Low ScvO2 is useful for titrating inotropes in cardiogenic
shock
• A low admission ScvO2 may predict higher mortality
CON
• Global measurement of oxygen delivery
• Transfusion of RBCs raises ScvO2 but doesn’t improve
sublingual microcirculatory flow
• May be elevated due to pathologic shunting
• Septic shock is due to cellular dysoxia, not hypoxia
Sources of Lactic Acid in Septic Shock
Anaerobic Metabolism (bowel/hepatic ischemia)
Acute Lung Injury/ARDS
Dysfunctional Cellular Metabolism
• Inactivation of Pyruvate Dehydrogenase
• NO suppression of mitochondrial respiration
• Excessive pyruvate production due to catecholamines
ICU Mortality and Time to Lactate
Clearance (< 2 mmol/L)
42.50%
45.00%
40.00%
35.00%
30.00%
Lactate Clearance:
A Better Goal Than
ScvO2?
25.00%
20.00%
15.00%
10.00%
5.00%
0.00%
3.90%
Less than 24
hours
More than 48
hours
Am J Surg 2001;182(5):481-5
Fill the Tank, but Forget the Filling Pressures
Bedside Ultrasound and Pulse Pressure
Variation are superior to CVP and PAOP for
guiding fluid resuscitation
Preload Responsiveness Doesn’t Always Mean
The Patient Needs Volume
“Warm around the edges” is a good rule to
follow
Transfuse Sparingly and Selectively
A hemoglobin >7 g/dL is usually OK
Raising the hematocrit may raise the SvO2,
but not necessarily tissue perfusion
Your attendings were right—treat the patient,
not the number
Markers of Dysoxia Are Better Than
Markers of Hypoxia
Septic shock is not a low-flow, low-oxygen
disease
Early aggressive resuscitation is key
Babies may be big at Baptist, but lactate is
also for the ICU
Division of Pulmonary, Critical Care, and Sleep Medicine
wowens@uscmed.sc.edu