download dit document - ICU

Neisseria Meningitidis5

"Except on fewoccasions,the patient appears todie from the body'sresponse to infectionrather than from it."Sir William Osler19046

Epidemiologie7

Severe Sepsis: Comparison WithOther Major Diseases (USA)Incidence of Severe SepsisMortality of SepsisCases/100,000AIDS* Colon BreastCancer § CHF † Sepsis ‡AIDS* Breast AMI † Sepsis ‡Cancer §†National Center for Health Statistics, 2001. § American Cancer Society, 2001. *American Heart Association.2000. ‡ Angus DC et al. Crit Care Med. 2001 and Wenzel N Eng J Med 2002

Severe Sepsis:A Growing Healthcare ChallengeTodayFuture>750,000cases of severesepsis/yearin the US *Sepsis Cases1,800,0001,600,0001,400,0001,200,0001,000,000800,000600,000400,000Severe Sepsis CasesUS Population600,000500,000400,000300,000200,000Total US Population/1,000100,000200,0002001 2025 2050Year*Angus DC. Crit Care Med. 2001

ACCP/SCCM Consensus Definitions• Infection– Inflammatory response tomicroorganisms, or– Invasion of normally steriletissues• Systemic InflammatoryResponse Syndrome (SIRS)– Systemic response to a varietyof processes• Sepsis– Infection plus– ≥2 SIRS criteria• Severe Sepsis– Sepsis– Organ dysfunction• Septic shock– Sepsis– Hypotension despite fluidresuscitation• Multiple Organ DysfunctionSyndrome (MODS)– Altered organ function in anacutely ill patient– Homeostasis cannot bemaintained without interventionBone RC et al. Chest. 1992;101:1644-55.

Microbiological eventInfectionSite of infectionCausativemicroorganism

Host responseInfectionSIRS- fever or hypothermia- tachycardia- leucocytosis or leucopenia- tachypnea

BurnsSepsisPancreatitisInfectionSIRSBAD ?TraumaALFOther

BurnsSepsisPancreatitisInfectionSIRSSevereSepsisTraumaSepticShockALFOther

Identifying Acute Organ Dysfunctionas a Marker of Severe SepsisAlteredConsciousnessConfusionPsychosisTachycardiaHypotension↑ CVP↑ PAOPTachypneaPaO 2

Mortality Increases with the Number of Organ DysfunctionsSevere sepsis = most frequent cause of death in the ICU90%80%70%60%50%40%30%20%10%0%One Two Three Four Five*Data from PROWESS (placebo arm). Eli Lilly, Data on File and Vincent JL, et al. Crit Care Med 1998;21:1793-800.*Four or more dysfunctional organs

Een aantalproblemen …19

1) Definitie van SIRS ….. en dusook van sepsis2) SIRS versus SEPSIS= is er al dan niet een infectie ??3) Sepsis patiënten vormen geenhomogene groep20

Definitie woord “bal” =een bolvormig voorwerp21

Definitie woord “bal” =een bolvormig voorwerp22

Host responseInfectionSIRS- fever or hypothermia- tachycardia- leucocytosis or leucopenia- tachypnea

2001 SCCM/ESICM/ACCP/ATS/SISInternational Sepsis Definitions Conference• Fever > 38°C• Hypothermia 90 bpm• Tachypnoe > 30 bpm• Significant edema/positive fluid balance> 20ml/kg over 24 hrs• Hyperglycemia in absence of DM• Leukocytosis > 12,000 µl• Leukopenia < 4,000 µl• Normal WBC with > 10% immature• CRP > 2 SD above normal value• Procalcitonine > 2 SD above nl value• Cardiac index > 3.5• Arterial hypoxemia P/F < 300• Acute oliguria < 0.5ml/kg for > 2 hrs• Creatinine increase > 0.5 mg/dl• Coagulation abnormalitiesaPTT > 60 sec, INR > 1.5• Thrombocytopenia < 100,000 µl• Hyperbilirubinemia > 4 mg/dl• Hyperlactatemia > 24 mg/dl• Ileus (absent bowel sounds)• Decreased capillary refill or mottling• Altered mental status• Arterial hypotension mean < 70 mmHg• Mixed venous oxygen sat < 70%24

2001 SCCM/ESICM/ACCP/ATS/SISInternational Sepsis Definitions Conference• Fever > 38°C• Hypothermia < 36°C• Heart rate > 90 bpm• Tachypnoe > 30 bpm• Significant edema/positive fluid balance> 20ml/kg over 24 hrs• Hyperglycemia in absence of DM25

2001 SCCM/ESICM/ACCP/ATS/SISInternational Sepsis Definitions Conference• Leukocytosis > 12,000 µl• Leukopenia < 4,000 µl• Normal WBC with > 10% immature• CRP > 2 SD above normal value• Procalcitonine > 2 SD above nl value• Arterial hypotension mean < 70 mmHg• Mixed venous oxygen sat < 70%26

2001 SCCM/ESICM/ACCP/ATS/SISInternational Sepsis Definitions Conference• Cardiac index > 3.5• Arterial hypoxemia P/F < 300• Acute oliguria < 0.5ml/kg for > 2 hrs• Creatinine increase > 0.5 mg/dl• Coagulation abnormalitiesaPTT > 60 sec, INR > 1.5• Thrombocytopenia < 100,000 µl• Hyperbilirubinemia > 4 mg/dl• Hyperlactatemia > 24 mg/dl• Ileus (absent bowel sounds)• Decreased capillary refill or mottling• Altered mental status27

1) Definitie van SIRS ….. en dusook van sepsis2) SIRS versus SEPSIS= is er al dan niet een infectie ??3) Sepsis patiënten vormen geenhomogene groep28

1) Definitie van SIRS ….. en dusook van sepsis2) SIRS versus SEPSIS= is er al dan niet een infectie ??3) Sepsis patiënten vormen geenhomogene groep30

Sepsis classificationConsensus Meeting Washington Dec 2001PTINRMO32

Sepsis classificationConsensus Meeting Washington Dec 2001Predisposing factorsInfectionResponsePatient withsepsisP 0 I 2 R 2 O 3Organ dysfunction33

Pathophysiologie34

Severe Sepsis:The Final Common PathwayEndothelial Dysfunction andMicrovascular ThrombosisHypoperfusion/IschemiaAcute Organ Dysfunction(Severe Sepsis)Death35

Behandeling36

BehandelingBehandeling van infectieHemodynamische stabilisatieOrgaan ondersteuningImmuno-modulatie37

Severe Sepsis Therapy: NumerousInvestigational ApproachesBacterial modulatorsAnti-endotoxinAnticytokinesIL-1ra, anti-TNF, sTNF-rAntiinflammatory agentsGlucocorticoids, leukocyte adhesion molecule inhibitorsHemostatic agentsRecombinant Human Activated Protein C, ATIII, TFPI, heparinOtheriNOS inhibition, antioxidants, thromboxane antagonists, bradykininreceptor antagonistsWheeler AP et al. N Engl J Med. 1999;340:207-14.38

Human Protein C300CHOCHO320EGFDomainCHO130KR150APCOOHAsp370CHO230HISSerSerineProteaseDomain40OH180Thrombincleavage siteNH 2Gla Domain39