SEPSIS

Respati S Dradjat , Bambang Wahjuprajitno

Tujuan
1. Mengetahui pathofisiologi sepsis 2. Menyadari peran prevensi, diagnosis dini dan pengobatan segera jauh lebih baik dibanding jika telah terjadi septik syok 3. Mengetahui peran antibiotika, pembedahan Mengetahui cara penatalaksanaan pasien sepsis

Definisi
Severe illness caused by overwhelming infection of the blood stream by toxinproducing bacteria

Sepsis = SIRS + documented source of infection

SIRS
Spektrum klinik disebabkan oleh respon immun karena infeksi atau trauma Terjadi inflamasi sistemik dan koagulasi sehingga terjadi disfungsi organ sampai multiple organ failure

Inflammatory Processes

Bacteremia Fungemia Viremia Others Adapted from Bone DC et al, 1992

Trauma Burn Pancreatitis Others

 SIRS accompanied by inability to regulate the inflammatory response The inflammatory system becomes hyperactive Involving both cellular and humoral defense mechanism Endothelial, epithelial cells, neutrophils, macrophages, lymphocytes, produce proinflammatory mediators TNF-a, IL-6, IL-1, IL-8

Sepsis
Inflammation Organ dysfunction Endothelial dysfunction Coagulation and fibrinolysis abnormalities Microvascular thrombosis DIC

Aktivasi inflamasi
Pelepasan Pro-inflammatory mediator TNF-, IL-1, IL-6, PAF Anti inflammatory mediators IL-4, IL10 Inflammatory mediator > tissue and diffuse capillary injury tissue function, damage, organ dysfunction

Koagulasi
Multiple inflammatory mediator promote coagulation Faktor XII berikatan dengan permukaan subendotel Aktivasi faktor XII mengaktifkan faktor XI Kompleks molekul terdiri aktivasi faktor IX, faktor VIII, Ca, dan fosfolipid, mengaktifkan faktor X Terbentuk trombin, akan mengubah fibrinogen menjadi fibrin

 IL-1a, IL-1b, TNF-, menyebabkan ekspresi TF pada endotel dan monosit memulai koagulasi TF berinteraksi dengan faktor VIIa, membentuk kompleks VIIa-TF, mengaktifkan faktor X dan IX Amplifikasi koagulasi melalui aktifasi faktor XI, VIII dan V

Fibrinolysis
Suppressed in sepsis Endotoxin PAI-1
Plasminogen Plasmin breakdown fibrin strand degrade fibrinogen+ coagulation factor V,VII

tPA ,proteinC , plasminogen

Sumber infeksi
Urinary tract infection Liver atau gall bladder Peritonitis Cellulitis Pneumonia Meningitis Osteomyelitis IV lines, surgical wound, drain, decubitus

Disfungsi organ
Ginjal Liver Paru CNS

SIRS
Pireksia atau hipotermia Takhikardia Takhipnoe Lekosit > 12.000 atau < 4.000

Systemic inflammatory respose syndrome

SIRS
Two or more of 1. Temperature >38 C or <36 C 2. Tachycardia >90/min 3. RR >20/min or PaCO2 ,4.3kPa 4. WBC>12X10 or < 4X10 or 10% immature form

Sepsis
Severe sepsis

SIRS due to infection

Sepsis with evidence of organ hypoperfusion
Severe sepsis with hypotension (SBP,90) despite adequate fluid resuscitation or the requirement for vasopressors/inotropes to maintain blood pressure

Septic shock

Pemeriksaan dan penatalaksanan

Pemeriksaan
Fever or hypothermia Hiperventilasi Kedinginan Gemetar Kulit hangat Skin rash Takhikardia Confusion or delirium Produksi urin menurun

Lab
Lekosit > atau < Platelet < Kultur darah + BGA asidosis Fungsi ginjal abnormal

Komplikasi
Syok septik Aliran darah pada organ vital rusak (Otak, Jantung, Ginjal) DIC

 Monitoring Antibiotika Terapi Supportive Oksigen IV fluid Medication Dialisis Ventilasi mekanik

Strategi penatalaksanaan

Management of Severe Bacterial Infection and Sepsis

Source Control

Nutrition / Metabolic Support

Resuscitation & Physiologic Support

Source Control
1. Remove / Treat Infection 2. Remove / Treat Inflammation 3. Remove Dead Tissue 4. Stabilization Injured Tissue 5. Restore Microcirculation

Nutrition / Metabolic Support

1. Achieve Nitrogen Balance 2. Avoid Calorie Overload 3. Avoid Long-Chain Fat Overload 4. Appropriate vitamins, Minerals, Trace Elements

Resuscitation & Physiologic Support

1. Minimize flow-dependent oxygen consumption 2. Minimize flow-dependent lactate clearance

Intervention
Multiple cellular target Wide spectrum Early Preventive Calculated

SIRS
TNF-blockade IL-1r antagonist IL-12 IL-10 / IL-13 Endotoxin neutralization Antibiotic Complement receptor blokade Inhibition of adhesion molecules ( anti-CD11b/CD18) PAF-receptor antagonist PG-synthetase inhibitor O2 radical scavenger

Autodestructive inflammation

Pasien stabil
Fluid Oxygen Nutrition Antibiotics Physiotherapy, DVT prophylaxis, drain management

Pasien tidak stabil

Undulating pyrexia Increasing white cell count Progressive tachycardia DIC Metabolic acidosis MOF

Penatalaksanaan MOF
Organ failure/dysfunction karena beratnya sepsis atau aktivasi respon inflamasi yang persisten Kardiovaskular, Pulmoner, Renal, Usus, Hematologi, SSP Kegagalan 3/> organ mortalitas menjadi 80-100%

Support as far as possible each organ system

Ventilation Hemofiltration/hemodialysis Inotropic support Nutritional support Blood product

Gagal paru
Disebabkan oleh Infeksi atau ARDS Inflamasi diffuse pada kedua paru Paru dipenuhi oleh sel dan cairan ekstravasasi karena inflamasi Paru sulit mengembang Breathless, progressively tachipnoeic, hypoxic dan cyanotic X-ray infiltrat di kedua paru

Gagal kardiovaskuler
Kehilangan tonus vaskuler perifer Kehilangan volume sirkulasi karena kebocoran kapiler Depresi miokard Fluid loading dan inotropic support

Gagal ginjal
Sering terjadi pada awal MOF Perbaiki perfusi dan oksigenasi sampai fungsi ginjal kembali

Organ lain
Usus, Otak, pembekuan darah Karena pengaruh proses patologi atau pembedahan, inflamasi sistemik dan hipoksia

Infeksi nosokomial
Endogenous Avoid superinfection or antibiotic resistance

Terapi antibodi monoklonal

Antagonist to endotoxin, TNF, IL-1 Have not reduced mortality, one component is removed, another mediator will continue

Nidus of Infection
Abscess Pneumonia Peritonitis Pyelonephritis Cellulitis

Organism

Exotoxin
TSST-1 Toxin A Structural Component Teichoic acid antigen Endotoxin

Plasma
Monocyte or Macrophages Endothelial Cells Neutrophils

Endogenous Mediators
Cytokines Arachidonic acid metabolites TNF Cyclooxygenase Prostaglandins IL-1, 2, 6, 8, Lypoxygenase Leukotrienes PAF Complement C5a Endorphins Kinin Endothelium-derived relaxing factor Coagulation Myocardial depressant substance

Myocardium
Depression Dilatation

Vasculature
Vasodilatation Vasoconstriction Leukocyte aggregation Endothelial-cell dysfunction SHOCK Multiple-Organ-System Failure Death

Organ (Kidney, Liver, Lung, Brain)

Dysfunction Metabolic defect

Refractory hypotension

Recovery

PREVENSI
Preoperatif ; optimalkan kesehatan umum pasien Perioperatif ; antibiotika profilaksis, operasi tidak berlama-lama, clean dan hemostasis yang baik, operasi elektif dan cegah hipotermia Pasca-operasi ; monitor, waspada hipoksi dan hipovolemi tersembunyi

TERIMA KASIH