immun-septicshock-2014

8/10/2019 immun-septicshock-2014

1/39

IMMUN-SEPSIS

Prof. Dr. Djoni Djunaedi, dr, SpPD, KPTI,

FINASIM


2/39

Definitions used to describe the condition of septic patients

Bacteriemia Presence of bacteria in blood (positive blood cultures)

Septicemia Presence of microbes or their toxins in blood

SIRS 2 of these conditions: fever (oral temp. >380C) or hypothermia (24 breath/min);tachycardia (heart rate > 90 beats/min); leukocytosis (> 12.000/L); leukopenia (< 4.000/L) or > 10%bands; may have a noninfectious etiology

Sepsis SIRS that has a proven or suspected microbial etiology

Severe sepsis = sepsis syndrome: sepsis with 0ne or more signs oforgan dysfunction, e.g:1. Cadiovascular: arterial systolic blood pressure 90mmHg or mean arterial pressure 70mmHg that

respons to administration of intravenous fluid

2. Renal: urine output < 0,5mL/kg per hour for 1 h despite adequate fluid resuscitation3. Respiratory: PaO2/FIO2 250 or, if the lung is the only dysfunction organ, 200

4. Hematologic: platelet count < 80.000/L or 50% decrease in platelet count from highest valueercorded over previous 3 days

5. Unexplained metabolic acidosis: a pH 7,30 or a base deficit 5,0mEq/L and a plasma lactate level> 1,5 times upper limit of normal for reporting lab

6. Adequate fluid resuscitation: pulmonary artery wedge pressure 12mmHg or CVP 8mmHg

Septic shock Sepsis with hypotention (arterial blood pressure < 90mmHg systolic, or 40mmHg less than patientsnormal blood pressure) for at least 1 h despite adequate fluid resuscitation; or need for vasopressors to

maintain systolic blood pressure 90mmHg or mean arterial pressure 70mmHg

Refractory

septic shock

Septic shock that last for > 1 h and does not respond to fluid or pressor administration

MODS Dysfunction of mor than one organ, requiring intervention to maintain homeostasis

SIRS: systemic inflammatory response syndromeMODS: multiple-organ dysfunction syndrome


3/39

Etiology

Microorganism and condition that may predispose to infection

Microorganism ConditionGram-negative bacteria:Enterobacteriaceae, pseudomonads, Haemophillus spp.,

other gram-negative bacteria

Diabetes mellitus

Lymphoproliferative diseases

Cirrhosis of the lever

Burns

Invassive procedures or devices

Neutropenia

Indwelling urinary catheterDiverticulitis, perforated viscus

Gram-positive bacteria:Staphylococcus aureus, coagulase-negative

staphylococcus, enterococci, Streptococcus pneumoniae,

other streptococci, other gram-positive bacteria

Intravascular catheter

Indwelling mechanical devices

Burns

Neutropenia

Intravenous drug use

Infection with superantigen-producing S. pyogenes

Fungi Neutropenia

Broad-spectrum antimicrobial therapy

Polymicrobial

Classic pathogens:Neisseria meningitidis, S. pneumoniae, H. influenzae,

Streptococcus pyogenes


4/39

Epidemiology

Incidence of sepsis and septic shock over the past 20 years

Annual number of cases: > 300.000

2/3 of cases occur in pts hospitalized for other illnesses The increasing incidence of severe sepsis is attributable to:

The aging of the population

The increasing longevity of pts with chronic diseases

The relatively high frequency with which sepsis develops in pts with AIDS

The wide spread use of antimicrobial agents, glucocorticoids, indwelling

catheter and mechanical devices and mechanical ventilation


5/39

Imunopatogenesis

Sistem imun pada pasien sepsis:

Immunosuppressive

Delayed hypersensitivity (-)

Kemampuan menghilangkan infeksi (-)

Predisposisi infeksi nosokomial


6/39

(Adaptasi dari Bochud, 2003, hlm 263)


7/39


8/39

Respons patogen dan cross-talk antar sel imun

Adaptasi dari Hotchkiss, 2003, hlm. 140


9/39

Infection

Endotoxin and other microbial toxins

Proinflammatory state with cytokine releaseand

Other proinflammatory mediators

Sepsis / SIRS

Shock and multiorgan dysfunction and possible death

Old paradigm of sepsis

Adaptasi dari Bone, 1997, hlm 239


10/39

Local anti-inflammatory

responseInitial insult

(bacterial, viral,traumatic, thermal)

Local pro-inflammatory

response

Systemic spillover of pro-

inflammatory mediators

Systemic spillover of anti-

inflammatory mediators

Systemic

reaction:SIRS (pro-inflammatory)

CARS (anti-inflammatory)

MARS

(mixed)

New paradigm of sepsis

Cardiovascular

compromise

C

(shock)

SIRS

predominates

H

Homeostasis

CARS and

SIRS balanced

A

Apoptosis

(cell death)

SIRS

predominates

O

Organ

dysfunction

SIRS

predominates

SSuppression

of theimmune system

CARS

predominates

Adaptasi dari Jacobi, 2002, suppl 5


11/39


12/39

(Adaptasi dari Bone, 1997, hlm 238)

TNF-

IL-1

IL-2

IL-6IL-8

IL-15

Neutrophil elastase

IFN-

Protein kinase

MCP-1*

MCP-2Leukemia inhib.factor

(D-factor

Thromboxane

Platelet activating factor

Soluble Adhesion mol.

Vasoactive neuropeptidesPhospholipase

Tyrosine kinase

Plasminogen activator inhib.-1

Free radical generation

Neopterin

CD14

Prostacyclin

Prostaglandins

IL-1 ra

IL-4

IL-10IL-13

Type II IL-1 receptor

Transforming growth factor-

Epinephrine

Soluble TNF- receptors

Leukotriene B4-receptor

antagonismSoluble recombinant CD-14

LPS binding protein

MCP = monocyte chemoattractant protein

Berbagai jenis molekul pro- dan anti-inflamasi

Proinflammatory molecules Anti-inflammatory molecules


13/39


14/39


15/39


16/39


17/39


18/39


19/39


20/39


21/39


22/39


23/39


24/39


25/39


26/39


27/39


28/39


29/39


30/39

?

Otopsi

Limfosit, epitel sel usus: menghilang (apoptosis)

Sel imun adaptif turun secara progresif dan dalam

jumlah besar

Penyebab kematian (gagal organ), secarahistologis: tidak sesuai

cell hibernation

(cell stunning)


31/39

Konsep baru dalam penatalaksanaan sepsis(Dellinger, 2004: Evidence-based)

1. Initial resuscitation and fluid therapy

Tujuan: memperbaiki oksigenasi jaringan (keseimbangan oxygendeliverydemand)

Follow up: konsentrasi, base defisit, pH, saturasi oksigen vena

sentral 6 jam pertama sangat menentukan keberhasilan tindakan

2. Diagnosis

Penting menentukan sumber dan mikroba penyebab infeksi

Bahan yang diperiksa: darah, urin, cairan serebrospinal, luka, sputum, dll

3. Antibiotic therapy

sebelum tersedia hasil kultur: sesuai pola antibiotika se-tempat


32/39

4. Source control

Drainase abses, debridement jaringan nekrosis

Alat bantu (kateter, dll), benda potensial sumber infeksidisingkirkan

5. Vasopressors

Diberikan selama pemberian fluid chalengge dan hipovolemik belumteratasi

Pemberian dopamin harus dalam dosis teurapetik

6. Inotropic therapy Bagi pasien dengan isi semenit rendah: beri dopamin

Bagi pasien dengan tekanan darah rendah: kombinasi dengan

vasopresor


33/39

7. Steroid

Pemberian dosis tinggimemperjelek kondisi (infeksi sekunder)

Temuan penelitian: pemberian hidrokortison 200- 300mg/hr selama 1

mingguperbaikan kondisi

Perlu pemberian dosis rendah kortikosteroid (Dellinger, 2004; Hotchkiss, 2003)

Kortikosteroid tidak direkomendasikan (Chambers, 2003)

8. Activated protein C

Pemberian Rh APC

Relative risk of death 19,4%; absolut risk of death 6,1%

Harus memenuhi sistem scoring APACHE

Rh APC:

Menghambat faktor Va dan VIIIa

trombin tak terbentuk

penghambatan aktivitas trombosit, pematangan neutrofil,

degranulasi sel mast

Pumya kemampuan direct anti-inflammatory

Dosis 24 g/kgBB/jam selama 96 jam

Efek samping: perdarahan (intrakranial: 3,4%)


34/39


35/39

12. Glucosa control

Mortalitas pasien dengan kadar gula darah normal < pasien dengan

kadar gula darah tinggi

Mekanisme protektif insulin belum dikerahui secara pasti

Koreksi hiperglikemiadaya fagositosis + efek anti-apoptotic

Insulin mencegah apoptotic cell death melalui aktivasi

phosphatidylinositol 3-kinase-Akt pathway (Siegel, 2002)

13. Renal replacement

Melalui continuous hemofiltration, intermittent hemodialysis

gagal ginjal akut

14. Bicarbonate therapy (masih memerlukan penelitian)


36/39

15. Deep vein thrombosis (DVT) prophylaxis

Pasien dengan kemungkinana DVT: beri low-dose unfractionatedheparin / low-molecular weight heparin

Pasien dengan resiko perdarahan:pakai intermittent compression

device e.g.

Trombositopenia

Koagulasi

Perdarahan aktif

16. Stress ulcer prophylaxis

Diberikan kepada semua pasien sepsis parah

Preparat: H2 receptor inhibitor

Efektivitas proton pump inhibitor belum pasti


37/39

Supplemental oxygen endotracheal

intubation and mechanical ventilation

Central venous and arterial

catheterization

Sedation, paralysis (if

intubated), or both

Goal achieved

ScvO2

MAP

CVP Crystalloid

Hospital admission

Colloid

Vasoactive agents

Transfusion of red cellsuntil hematocrit 30%

Inotropic agents


38/39

Kesimpulan

Terjadi pergeseran besar dalam sikap peneliti mengenai

masalah sepsis

Sepsis tidak sekedar immune system gone haywire

melainkan kemungkinan severely compromised immune

system (mikroba patogen )

Hasil otopsi menunjukkan focal necrosis

Evidence-based recommendation: initial resuscitation

stress ulcer prophylaxis

Future therapy: enhance / inhibit the patients immune

response, depending on genetic polymorphisms, duration of

disease, characteristic of particular pathogen


39/39

Documents

immun-septicshock-2014