Goal-Directed Therapy in Goal-Directed Therapy in Septic ShockSeptic Shock

What Goals Matter, What Don’t, What Goals Matter, What Don’t, and Why We Should Careand Why We Should Care

William Owens, MDWilliam Owens, MD

Division of Pulmonary and Critical Care MedicineDivision of Pulmonary and Critical Care Medicine

University of South CarolinaUniversity of South Carolina

DisclosuresDisclosures

I have no ties, financial or otherwise, with any companies or I have no ties, financial or otherwise, with any companies or products discussed today.products discussed today.

I do have biases, prejudices, and opinions completely I do have biases, prejudices, and opinions completely unfounded in fact, which I am always happy to share!unfounded in fact, which I am always happy to share!

Patients enrolled who had either:Patients enrolled who had either: SBP < 90 after a 20 mL/kg fluid bolus, orSBP < 90 after a 20 mL/kg fluid bolus, or Lactate > 4 mmol/LLactate > 4 mmol/L

46% vs 30%46% vs 30%

INTERVENTION ARMINTERVENTION ARM

GOAL: Fill The Tank!GOAL: Fill The Tank!

Pulmonary Pulmonary Artery CatheterArtery Catheter

Central Venous Central Venous PressurePressure

AUC 0.56AUC 0.56

MeasurementMeasurement PPVPPV NPVNPVCVP< 8CVP< 8 51%51% 65%65%CVP< 12CVP< 12 47%47% 67%67%CVP< 5CVP< 5 47%47% 58%58%PAOP< 11PAOP< 11 54%54% 74%74%PAOP< 11 + CVP< 8PAOP< 11 + CVP< 8 54%54%63%63%CVP< 8 + SVI< 30CVP< 8 + SVI< 30 61%61% 39%39%PAOP< 12 + SVI< 30PAOP< 12 + SVI< 30 69%69%58%58%

(PP(PPmaxmax – PP – PPminmin))

(PP(PPmaxmax + PP + PPminmin/2)/2)

PPV≥13% correlates with PPV≥13% correlates with preload responsiveness preload responsiveness

(AUC 0.91)(AUC 0.91)

* Tidal Volume should be 8 cc/kg* Tidal Volume should be 8 cc/kg* Breathing should be controlled * Breathing should be controlled and passiveand passive* Cardiac rhythm must be regular* Cardiac rhythm must be regular

12% change corresponds with fluid responsiveness12% change corresponds with fluid responsiveness

PPV 93%PPV 93% NPV 92%NPV 92%Feissel M, Michard F, Faller J, Teboul JFeissel M, Michard F, Faller J, Teboul JThe respiratory variation in inferior vena cava diameter as a guide to fluid The respiratory variation in inferior vena cava diameter as a guide to fluid therapytherapyIntensive Care Med (2004) 30: 1834-1837Intensive Care Med (2004) 30: 1834-1837

LVEDA < 10 cmLVEDA < 10 cm22 or LVEDA/BSA < 5.5 cm or LVEDA/BSA < 5.5 cm22/m/m22

corresponds with preload responsivenesscorresponds with preload responsiveness

GOAL: Fill The Tank!GOAL: Fill The Tank!

CVP is not accurate CVP is not accurate at any levelat any level

The PA catheter The PA catheter isn’t much betterisn’t much better

Ultrasound and PPV Ultrasound and PPV show promiseshow promise

Clinical Correlation Clinical Correlation Is Required!Is Required!

GOAL: Hemoglobin ≥ 10 g/dLGOAL: Hemoglobin ≥ 10 g/dL

CaOCaO22 = 1.34 × Hgb × = 1.34 × Hgb × SaOSaO22

DODO22 = CO × CaO = CO × CaO22 × 10 × 10

838 patients randomized838 patients randomized

Transfusion triggers of 7.0-9.0 g/dL Transfusion triggers of 7.0-9.0 g/dL versus 10.0-12.0 g/dLversus 10.0-12.0 g/dL

No difference in mortality overallNo difference in mortality overall

No difference in mortality in patients No difference in mortality in patients with coronary artery diseasewith coronary artery diseaseShockShockDrop in Hgb > 3 g/dLDrop in Hgb > 3 g/dLCoronary IschemiaCoronary Ischemia

Not Applicable to Initial Resuscitation?Not Applicable to Initial Resuscitation?

DODO22crit in animals seems to be 3-crit in animals seems to be 3-3.5 g/dL3.5 g/dL

Microcirculatory hematocrit is Microcirculatory hematocrit is relatively constant at 12-15%relatively constant at 12-15%

No necrosis at autopsyNo necrosis at autopsy

Healthy humans Healthy humans can tolerate can tolerate hemodilution to 5 hemodilution to 5 g/dLg/dL

Mathematical CouplingMathematical Coupling

Stored Blood Holds On To OxygenStored Blood Holds On To Oxygen

Supply Dependency Doesn’t Exist Supply Dependency Doesn’t Exist In Septic ShockIn Septic Shock

RBCs are depleted of 2-3 RBCs are depleted of 2-3 DPG until 24 hours after DPG until 24 hours after transfusiontransfusion

Free Hemoglobin scavenges NO—Free Hemoglobin scavenges NO—inflammation, vasoconstriction, inflammation, vasoconstriction, thrombosis, oxidative stressthrombosis, oxidative stress

Increasing blood viscosity causes vasodilation Increasing blood viscosity causes vasodilation via endothelium-released NOvia endothelium-released NO(much of the benefit of transfusion may be independent of (much of the benefit of transfusion may be independent of

CaOCaO22))

80%80% 95%95%

Marik showed that patients transfused stored Marik showed that patients transfused stored blood had consistently lower gastric mucosal blood had consistently lower gastric mucosal pHpH

(JAMA 1993;269(23):3024– 9)(JAMA 1993;269(23):3024– 9)

GOAL: Hemoglobin ≥ 10 g/dLGOAL: Hemoglobin ≥ 10 g/dL

No evidence for arbitrary No evidence for arbitrary transfusion triggertransfusion trigger

Transfused RBCs may Transfused RBCs may worsen microcirculatory worsen microcirculatory perfusionperfusion

Base decision to Base decision to transfuse on signs of transfuse on signs of inadequate oxygen inadequate oxygen deliverydelivery

• Rising lactateRising lactate• Elevated troponinElevated troponin• Ischemic ECG findingsIschemic ECG findings• Poor perfusion (i.e., the Poor perfusion (i.e., the cold cold big toe)big toe)

GOAL: Keep ScvOGOAL: Keep ScvO22 ≥ 70% ≥ 70%

VOVO22 = CO × 1.34 × Hgb × [SaO = CO × 1.34 × Hgb × [SaO22 –SvO –SvO22]]

Nguyen et al: ED Resuscitation Improves Nguyen et al: ED Resuscitation Improves Survival (Survival (Acad Emerg Med, 2000Acad Emerg Med, 2000))

PROPRO

• Low ScvOLow ScvO22 is useful for titrating inotropes in is useful for titrating inotropes in cardiogenic shockcardiogenic shock

• A low admission ScvOA low admission ScvO22 may predict higher mortality may predict higher mortality

CONCON

• Global measurement of oxygen deliveryGlobal measurement of oxygen delivery • Transfusion of RBCs raises ScvOTransfusion of RBCs raises ScvO22 but doesn’t improve but doesn’t improve sublingual microcirculatory flowsublingual microcirculatory flow

• May be elevated due to pathologic shuntingMay be elevated due to pathologic shunting

• Septic shock is due to cellular dysoxia, not Septic shock is due to cellular dysoxia, not hypoxiahypoxia

Sources of Lactic Acid in Septic ShockSources of Lactic Acid in Septic Shock

Anaerobic Metabolism (bowel/hepatic ischemia)Anaerobic Metabolism (bowel/hepatic ischemia)

Acute Lung Injury/ARDSAcute Lung Injury/ARDS

Dysfunctional Cellular MetabolismDysfunctional Cellular Metabolism• Inactivation of Pyruvate DehydrogenaseInactivation of Pyruvate Dehydrogenase• NO suppression of mitochondrial respirationNO suppression of mitochondrial respiration• Excessive pyruvate production due to catecholaminesExcessive pyruvate production due to catecholamines

Am J Surg 2001;182(5):481-5Am J Surg 2001;182(5):481-5

Lactate Clearance:Lactate Clearance:A Better Goal Than A Better Goal Than ScvOScvO22??

Fill the Tank, but Forget the Filling Fill the Tank, but Forget the Filling PressuresPressures

Bedside Ultrasound and Pulse Pressure Bedside Ultrasound and Pulse Pressure Variation are superior to CVP and PAOP Variation are superior to CVP and PAOP

for for guiding fluid resuscitationguiding fluid resuscitation

Preload Responsiveness Doesn’t Always Preload Responsiveness Doesn’t Always Mean Mean The Patient Needs VolumeThe Patient Needs Volume

““Warm around the edges” is a good rule Warm around the edges” is a good rule to to followfollow

Transfuse Sparingly and SelectivelyTransfuse Sparingly and Selectively

A hemoglobin >7 g/dL is usually OKA hemoglobin >7 g/dL is usually OK

Raising the hematocrit may raise the Raising the hematocrit may raise the SvOSvO22, , but not necessarily tissue perfusionbut not necessarily tissue perfusion

Your attendings were right—treat the Your attendings were right—treat the patient, patient, not the numbernot the number

Markers of Dysoxia Are Better Than Markers of Dysoxia Are Better Than Markers of HypoxiaMarkers of Hypoxia

Septic shock is not a low-flow, low-Septic shock is not a low-flow, low-oxygen oxygen diseasedisease

Early aggressive resuscitation is keyEarly aggressive resuscitation is key

Babies may be big at Baptist, but lactate Babies may be big at Baptist, but lactate is is also for the ICUalso for the ICU

Division of Pulmonary, Critical Care, and Sleep Division of Pulmonary, Critical Care, and Sleep MedicineMedicine

wowens@uscmed.sc.eduwowens@uscmed.sc.edu