current concept of pathophysiology of sepsis manutham manavathongchai md

Current concept of Current concept of pathophysiology of sepsispathophysiology of sepsis

Manutham Manavathongchai MD

ACCP/SCCM Consensus ACCP/SCCM Consensus definitionsdefinitions

• Systemic inflammatory responseSystemic inflammatory response syndrome ( SIRS)syndrome ( SIRS)

– Tachycardia, HR >2 SD, <1yr Tachycardia, HR >2 SD, <1yr bradycardiabradycardia

– Mean RR >2 SDMean RR >2 SD– WBC elevate or depressed for age WBC elevate or depressed for age – Core temp >38.5 Core temp >38.5 °°C or <36 C or <36 °°C C

one of two have to be abn Temp or WBCone of two have to be abn Temp or WBC


• InfectionInfection

– Inflammatory response to Inflammatory response to microorganisms, ormicroorganisms, or

– Invasion of normally sterile tissuesInvasion of normally sterile tissues


• SepsisSepsis– Infection plusInfection plus– SIRS criteriaSIRS criteria


• Severe SepsisSevere Sepsis– Sepsis Sepsis plusplus– Cardiovascular dysfunction Cardiovascular dysfunction oror– Acute respiratory distress syndrome Acute respiratory distress syndrome

(ARDS) (ARDS) oror– Other 2 organs dysfunctionOther 2 organs dysfunction

Organ dysfunctionOrgan dysfunction

• CardiovacularCardiovacular

• pulmonologicpulmonologic

• NeurologicNeurologic

• HematologicHematologic

• RenalRenal

• HepaticHepatic


• Septic shockSeptic shock– Sepsis Sepsis plusplus– Hypotension despite fluid resuscitation Hypotension despite fluid resuscitation

oror– Need vasoactive drugs Need vasoactive drugs oror– 2 organs dysfunction2 organs dysfunction

SepsisSepsis

Adapted from: Bone RC et al. Chest. 1992;101:1644-55.Opal SM et al. Crit Care Med. 2000;28:S81-2.


• Multiple Organ Dysfunction Multiple Organ Dysfunction Syndrome (MODS)Syndrome (MODS)

– Altered organ function in an acutely ill Altered organ function in an acutely ill patientpatient

– Homeostasis cannot be maintained Homeostasis cannot be maintained without interventionwithout intervention

Early sepsisEarly sepsis

• Innate system (non specific)Innate system (non specific)

• Adaptive system (specific)Adaptive system (specific)

Innate system (non specific)Innate system (non specific)

• Cell adhesion moleculesCell adhesion molecules

• Procoagulants and anticoagulantsProcoagulants and anticoagulants

• Nitric oxide synthaseNitric oxide synthase

Russel JA. N Engl J Med 2006;355:1699-713

Ann Emerg Med. 2006;48:28-54

SYSTEMIC ACTIVATION OF COAGULATION

Intravascular deposition of fibrin

Thrombosis of small and midsize vessels

Organ failure

Depletion of plateletsand coagulation factors

Bleeding

DEATHDEATH

Septic shockSeptic shockRole of NORole of NO

• Infection induce NOS expressionInfection induce NOS expression

• High level Help eradicate infection butHigh level Help eradicate infection butAlso cAlso cause ause vasodilation/ Massive vasodilation/ Massive hypotensionhypotension

Samjot S et al Chest 2005;128:1706

Activated protein c in Pediatric Activated protein c in Pediatric septic shockseptic shock P<0.01, n=30

60

50

40

30

20

10Act

ivat

ed p

rote

in C

act

ivity

Survivors Non-Survivors

Samransamruajkit et al ATS 2005Samransamruajkit et al ATS 2005

Adaptive system (specific)Adaptive system (specific)

• Cell-mediated response (T-cells)Cell-mediated response (T-cells)

• Humoral response (B-cells)Humoral response (B-cells)

Organ dysfunctionOrgan dysfunction

• Circulatory dysfunction: redistribution of bl Circulatory dysfunction: redistribution of bl flow flow

: vascular resistance : vascular resistance

: myocardial contraction : myocardial contraction

• Acute lung injury : microvascular permeabilityAcute lung injury : microvascular permeability

• Liver, kidney , CNS dysfunctionLiver, kidney , CNS dysfunction

Septic shock stage/CourseSeptic shock stage/Course

“Irreversible Phase”

“Irreversible Phase” “Reversible

Phase”

“ReversiblePhase”

“Early Warm Shock”

“Early Warm Shock”

Early resuscitationEarly resuscitation Aggressive RxAggressive Rx Paliative RxPaliative Rx

Septic shockSeptic shockGeneral principle summaryGeneral principle summary

**PreventionEarly

RecognitionImmediateResuscitation Stabilization

EarlyRecognitionWarm ShockReversiblesigns of hypoPerfusionWide PPUO

ImmediateResuscitation1 st HRResuscitationABCVolumeInotropeSteroids

StabilizationHemodynamic supportAppropriateInotrope useClose monitoringNutrition

PreventionProphylacticAbxP IatrogenicVaccine

current concept of pathophysiology of sepsis manutham manavathongchai md

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