SEPSISan OverviewDoni Priambodo Wijisaksono

Subdivision of Tropical Medicine and Infectious DiseasesInternal Medicine DepartmentFaculty of Medicine Gajah Mada University / Dr Sardjito General Hospital Jogjakarta

Microorganisms represent the first species of living organisms that populated our planet and will probably continue to survive well beyond the extinction of the human race

(Fasano, 2002)

www.themegallery.comSevere Sepsis: A Significant Healthcare Challenge1Major cause of morbidity and mortality worldwide Leading cause of death in noncoronary ICU (US)* 11th leading cause of death overall (US) 2About 1,000,000 cases of severe sepsis in US annually3In the US, about 600-1000 patients die of severe sepsis daily*Sands KE et al. JAMA. 1997;278:234-40; Based on data for septicemia. Murphy SL. National Vital Statistics Reports. Angus DC et al. Crit Care Med. 2001 (In Press); reflects hospital-wide cases of severe sepsis as defined by infection in the presence of organ failure.

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Severe Sepsis is a Significant Healthcare Burden Sepsis consumes significant healthcare resources.

In a study of Patients who contract nosocomial infections, develop sepsis and survive:ICU stay prolonged an additional 8 days.Additional costs incurred were $40,890/ patient.

Estimated annual healthcare costs due to severe sepsis in U.S. exceed $16 billion !!!

Cannon et al, US, 2012 :

Mortality rate of severe sepsis: 20% Mortality rate of septic shock: 45% Sardjito General Hospital Jogjakarta : In recent 2 years: mortality rate of severe sepsis: 31% mortality rate of septic shock: 64%

Martin et al, NEJM 2003; 348:1546

Definisi Sepsis adalah: adanya bukti atau kecurigaan kuat adanya infeksi, yang disertai tanda-tanda sindroma respon inflamasi sistemik (SIRS: Systemic Inflammatory Response Syndrome) yang meliputi 2 atau lebih tanda di bawah ini:

- suhu badan 38C, atau 36C- nadi 90 kali/menit- respirasi 20 kali/menit atau P CO2 arteri < 32 mmHg- angka lekosit 12000/mmk atau 4000/mmk atau sel lekosit muda > 10%

*Sepsis: A Complex DiseaseThis Venn diagram provides a conceptual framework to view the relationships between various components of sepsis.Adapted from: Bone RC et al. Chest. 1992;101:1644-55.Opal SM et al. Crit Care Med. 2000;28:S81-2.

*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 SepsisAdapted from: Bone RC, et al. Chest 1992;101:1644Opal SM, et al. Crit Care Med 2000;28:S81

www.themegallery.comACCP/SCCM Consensus Definitions

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Question: Why do Septic Patients Die?

Answer: Organ Failure

APCCD 4+TCRSUPER ANTIGENIL - 10 IL - 4IL - 5IL - 6

IgTH - 2TH - 1B cellCD 8+IL-2CSFCompl.N NKTF-VIIA IFN - gIMUNOPATOGENESISLPS bp

CD 14IL 6TNF - IL -1NOICAM -1aLPSIMUNO.COMSEPSISMODSHOCKSEPTIC(Guntur, 2000)C3a, C5aPGE 2TLR 4TLR2C7aPaI-1IL 8

Pathogenesis of sepsis: changes in the circulation during sepsisWong et al, Gut 2005;54;718-725

Surviving sepsis campaign guidelines for management of severe sepsis and septic shock DiagnosisInitial ResuscitationAntibiotic therapySource ControlFluid TherapyVasopressorsInotropic TherapySteroids Recombinant Human Activated Protein CBlood Product AdministrationMechanical Ventilation of Sepsis-Induced Acute Lung Injury

Sedation, Analgesia, and Neuromuscular Blockade in SepsisGlucose ControlRenal ReplacementBicarbonate therapyDeep Vein Thrombosis ProphylaxisStress Ulcer ProphylaxisConsideration for Limitation of SupportPediatric considerationDellinger RP - Crit Care Med 2008; 32(3): 858-73

SummarySepsis: Significant Healthcare Challenge & Burden

The complexity of Sepsis: Organisms,Pathophysiology and Management

**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 blood streamSeptic 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 interventionInflammation and hemostasis are tightly linked. Therefore, although not shown on this slide, sepsis and severe sepsis lie on a background of disturbed hemostasis.

Bone 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.