SEPSISdr. Donnie Lumban Gaol, SpPD
Sepsis the Greek word for putrificationDenoted tissue breakdown that resulted in illness SEPSISEPIDEMIOLOGIMORTALITAS DAN MORBIDITASETIOLOGIDEFINISIMANIFESTASI KLINIKPATOGENESISDIAGNOSISPENATALAKSANAAN
1995: 6 million records analyzed from 7 states750,000 cases of severe sepsis occur annually ( 3/ 1000)Mortality 28.6% or 250,000 deathsProjected increase by 1.5% per yearAngus et al , CCM 2001, 29: 1303-1310SEPSISEPIDEMIOLOGIMORTALITAS DAN MORBIDITASETIOLOGIDEFINISIMANIFESTASI KLINIKPATOGENESISDIAGNOSISPENATALAKSANAAN
MORTALITAS DAN MORBIDITASAngka mortalitas secara keseluruhan sekitar 28.6%, setara dengan 215.000 kematian tiap tahun di Amerika Serikat.
Faktor-faktor yang mempengaruhi pada awal kematian adalah jumlah sistem organ yang terlibat, rendahnya pH darah arteri, dan skor SAPS, MEDS24 atau APACHE yang tidak baik
Angus DC, et al. Crit Care Med 2001MortalitySeptic Shock53-63%20-53%Severe Sepsis300,0007-17%Sepsis400,000 IncidenceBalk, R.A. Crit Care Clin 2000;337:52Mortalitas Meningkat Pada Pasien Syok SeptikApproximately 200,000 patients including 70,000 Medicare patients have septic shock annually
Severe Sepsis: Comparative Incidence and MortalityAngus DC, et al. Crit Care Med 2001; American Cancer Society
MortalityDeaths/YearSepsis is a common condition. In the US, the incidence of sepsis per 100,000 exceeds AIDS, breast cancer, and first myocardial infarctions. Concerted public awareness campaigns have emphasized the importance of coronary heart disease, AIDS, and breast cancer. Yet, as shown on this slide, the mortality of severe sepsis exceeds AIDS, breast cancer and is only slightly less that that of patients dying suddenly of an acute myocardial infarction.9Sepsis is a common condition. In the US, the incidence of sepsis per 100,000 exceeds AIDS, breast cancer, and first myocardial infarctions. Concerted public awareness campaigns have emphasized the importance of coronary heart disease, AIDS, and breast cancer. Yet, as shown on this slide, the mortality of severe sepsis exceeds AIDS, breast cancer and is only slightly less that that of patients dying suddenly of an acute myocardial infarction.
Angus DC, Linde-Zwirble WT, Lidicker J, et al. Incidence, cost and outcomes of severe sepsis in the United States. Crit Care Med 2001; American Heart Association. 2001 Heart and Stroke Statistical Update. Dallas, Tex: American Heart Association, 2000.American Cancer Society. Cancer Statistics. Online edition, accessed 3/29/01.
Mortality of Severe Sepsis by Age in the United StatesAngus DC, et al. Crit Care Med 2001.0%5%10%15%20%25%30%35%40%45%01510152025303540455055606570758085AgeMortalityWithout Co-morbidityWith Co-morbidityOverall10Severe sepsis shows a small peak in incidence in the very young (38 C or < 36 CHR> 90/ minRR> 20/ min or PaCO2< 32mmHgWBC> 12,000 or < 4,000, or > 10% immature (bands) formsBone RC, CHEST 1992: 101(6):1644-55 DefinitionsSepsis Systemic inflammatory response to known or suspected infection Severe Sepsis SIRS associated with organ dysfunction (failure), hypoperfusion, and perfusion abnormalitiesBone, R et al. Chest 1992;101:1644Definitions ContinuedSeptic shock A subset of severe sepsis, where patients experience combined decreased systemic vascular resistance and the presence of reduced myocardial performanceBone, et al. CHEST , 1992;101:1644
Sepsis: Defining a Disease Continuum A clinical response arising from a nonspecific insult, including 2 of the following:Temperature 38oC or 36oCHR 90 beats/minRespirations 20/minWBC count 12,000/mm3 or 4,000/mm3 or >10% immature neutrophilsSIRS = Systemic Inflammatory Response SyndromeSIRS with a presumed or confirmed infectious processSepsisSIRSInfection/TraumaSevere SepsisBone RC, et al. Chest 1992;101:1644Opal SM, et al. Crit Care Med 2000;28:S81Sepsis: Defining a Disease ContinuumBone et al. Chest 1992;101:1644; Wheeler and Bernard. N Engl J Med 1999;340:207SepsisSIRSInfection/TraumaSevere SepsisSepsis with 1 sign of organ failureCardiovascular (refractory hypotension)RenalRespiratoryHepaticHematologicCNSMetabolic acidosisShockBone et al. Chest 1992;101:1644Relationship Of Infection, SIRS, Sepsis Severe Sepsis and Septic ShockSIRSINFECTIONPANCREATITISBURNSTRAUMAOTHERSEPSISSEVERESEPSISSEPTICSHOCK22Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644-55.Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med 2000;28:S81-2.This conceptual framework shows the interrelationships between infection, non-infectious disorders, SIRS, sepsis and severe sepsis. Components of the process not discussed on the following slides include:Infection: a microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organismsBacteremia: the presence of viable bacteria in the bloodstreamSeptic shock: sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include, but are not limited to, lactic acidosis, oliguria or an acute alteration in mental status Multiple organ dysfunction syndrome (MODS): presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without interventionSevere Sepsis: Primary SourcePulmonary: 50%Abdomen/Pelvis: ~25%Primary bacteremia: ~15%Urosepsis: 10%Skin: 5%Vascular: 5%Other: ~15%Martin GS, et al. NEJM 2003;348:1546
Manifestasi Klinik Vital SignFever, Chills/Rigors, HypotermiaTachycardiaTachypneaCentral Nervous SystemEncephalopathyCardiopulmonaryIncreased Cardiac outputDecreased systemic vascular resistanceHypotensionMetabolic asidosis hyperlactatemiaAcute Lung injury, HypoxemiaVincent LJ.et.al. The Sepsis Text. Kluwer Academic Publisher 2002 Manifestasi Klinik RenalDecreased urinary outputElevated BUN and creatinineGastrointestinalIleusElevated Bilirubin, predominantly direct fractionDermatologyEcthyma gangrenosumRash-maculopapular, vesicular, BullousToxic erythemaMetabolicHyperglicemia, hypoglicemiaHematologicLeukocytosis, leukopenia, thrombocytopenia, DIC
Vincent LJ.et.al. The Sepsis Text. Kluwer Academic Publisher 2002
Bone, RC, Crit Care Med 1996; 24:1125.
Sepsis Battlefield: Cells and MediatorsHotchkiss RS, Karl IE, NEJM 2003;348:13831The pathophysiology of sepsis depends on a complex interaction and cooperation between a whole host of cells, including neutrophils, macrophages and structural cells such as endothelial cells, epithelial cells, and dendritic cells.This slide illustrates the response to pathogens, involving cross-talk among many immune cells, including macrophages, dendritic cells and CD4 T cells.Macrophages and dendritic cells are activated by the ingestion of bacteria and by stimulation through cytokines secreted by CD4 T cells. These cells secrete a variety of cytokines, chemokines and lipid mediators which can attract further immune cells into the battlefield.The concept has emerged that although initially sepsis may be characterized by increases in inflammatory mediators, as the sepsis persists, there is a shift toward an anti-inflammatory immunosuppressive state.Alternatively, CD4 T cells that have an anti-inflammatory profile (type 2 helper T cells) secrete IL-10, which suppresses macrophage activation.The factors that determine whether CD4 T cells have Th1 (inflammatory) or Th2 (anti-inflammatory) responses are unknown but appear to be influenced by the type of pathogen, size of the bacterial inoculum and the site of infection.Casualties in this battle are the host cells: endothelial cells, epithelial cells in organs such as the lung, kidney and gut and parenchymal cells such as cardiac myocytes.It also has become clear that during sepsis, T cells become anergic or lose their ability to proliferate or secrete cytokines in response to specific antigens. This sepsis-induced anergy seems to be triggered by apoptotic or programmed cell death. Basically, the cells commit suicide by the activation of proteases that disassemble the cell. In the case of lymphocytes, a potential mechanism of apoptosis may be stress-induced endogenous release of glucocorticoids.Inflammatory Responses to SepsisRussel JA. Management of Sepsis. N Eng J Med 2006;355:1699-713
Pathogenesis of Severe SepsisInfectionMicrobial Products(exotoxin/endotoxin)Cellular ResponsesOxidasesPlateletActivationKininsComplementCoagulopathy/DICVascular/Organ System InjuryMulti-Organ FailureDeathEndothelial damageEndothelial damageCoagulationActivationCytokinesTNF, IL-1, IL-63535
Biologic effects of proinflammatory cytokines such as TNF and IL-1
Fever Hypotension Acute phase protein response Induction of IL-6 and IL-8 Coagulation activation Fibrinolytic activation Leukocytosis Neutrophil degranulation and augmented antigen expression (TNF) Increased endothelial permeability (TNF) Stress hormone response Enhanced gluconeogenesis (TNF) Enhanced lipolysis (TNF)
Severe Sepsis:Initial Resuscitation (1st 6 hours)Should begin as soon as the syndrome is recognized and should not be delayed pending ICU admission.Elevated serum lactate concentration identifies tissue hypoperfusion in patients at risk who are not hypotensive.Resuscitation GoalsGoals in the first 6 hours:CVP: 8-12 mm HgMAP > 65 mm HgUrine output > 0.5 ml/kg/hrCentral venous (SVC) or mixed venous oxygen (SvO2) saturation > 70%
6 Hour Resuscitation BundleEarly IdentificationEarly Antibiotics and CulturesEarly Goal Directed Therapy
SSCSeptember 2005416 - hou