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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
ACCP/SCCM Consensus ACCP/SCCM Consensus definitionsdefinitions
• InfectionInfection
– Inflammatory response to Inflammatory response to microorganisms, ormicroorganisms, or
– Invasion of normally sterile tissuesInvasion of normally sterile tissues
ACCP/SCCM Consensus ACCP/SCCM Consensus definitionsdefinitions
• SepsisSepsis– Infection plusInfection plus– SIRS criteriaSIRS criteria
ACCP/SCCM Consensus ACCP/SCCM Consensus definitionsdefinitions
• 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
ACCP/SCCM Consensus ACCP/SCCM Consensus definitionsdefinitions
• 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.
ACCP/SCCM Consensus ACCP/SCCM Consensus definitionsdefinitions
• 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
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