kuliah sepsis

7/27/2019 Kuliah Sepsis

1/38

Divisi Penyakit Tropik - Infeksi

Lab/SMF Ilmu Penyakit Dalam

SEPSIS &

SEPTIC SHOCK


2/38

Terminologi

Infeksi :

beradanya microorganisme seperti bakteri, jamur,

virus, protozoa, dengan disertai respon inflamasi

dan multiplikasi dari organisme tersebut, padajaringan Host yang dalam keadaan normal

seharusnya steril

Bakteremia :

adanya bakteri viabeldalam darah


3/38

SIRS (Systemic Inflammatory Response Syndrome) :

Respon Inf lamasi Sistemik terhadap berrbagai cl in ical insult

yang berat, ditandai oleh dua atau lebih g ejala-gejala berikut

:

Suhu tub uh > 38o

C atau < 36o

CDenyut jantung > 90 / menit

Respirasi > 20 / menit atau PaCO2

< 32 mm Hg

Sel darah puti h > 12.000 / mm3atau

< 4000 / mm3, atau > 10% ben tuk imatur (stab= band )

Sepsis: SIRS yang penyebabnya karena infeksi

Terminologi


4/38

Terminologi

Severe Sepsis :

Sepsis yang disertai gangguan fungsi organ,hipoperfusi atau hipotensi

Septic Shock :

Sepsis dengan h ipotensi (sisto l ik < 90 mm Hg ataupenu runan 40 mm Hg dari data dasar), setelah

pemberian cairan resus itasi yang adekwat, disertai

tanda-tanda hipoperfusi

MODS (Multiple Organ Dysfunction Syndrome) :Gangguan fungsi organ pada seorang yang sakitberat, dimana homeostasis tidak dapatdipertahankan tanpa intervensi


5/38

Hubungan SEPSIS dan SIRS

Infection

SIRS

Burn

Trauma

Pancreatitis

DM

Surgical

Sepsis

Severe

Sepsis

MOF


6/38

SEPSIS: DEFINING A DISEASE CONTINUUM

A clinical response arisingfrom a nonspecific insult,including 2 of the following:

Temperature 38oC or 36oC

HR 90 beats/min

Respirations 20/min

WBC count 12,000/mm3 or4,000/mm3 or >10% immatureneutrophils

SIRS = systemic inflammatory response syndrome.

Bone et al. Chest. 1992;101:1644.

SIRS related toinfection (suspectedor confirmed)

SepsisSIRSInfection/Trauma Severe Sepsis


7/38

SEPSIS: DEFINING A DISEASE CONTINUUM

Bone et al. Chest. 1992;101:1644; Wheeler and Bernard. N Engl J Med. 1999;340:207.

SepsisSIRSInfection/Trauma

Severe Sepsis

Sepsis with organ failure(one or more)

Cardiovascular(hypotension)

Renal

Respiratory

Hepatic

Hematologic

CNS

Unexplained metabolicacidosis


8/38

Injury Infection

Non Infection

LPS ( lipopolysaccharide )

Complement System

Phagocyte cellsRapid Inflammatory Reaction

Monocytes and Macrophages

Sitokine pro inflammatory

secretion

Inflammatory Cascade

(Mediator, Neutrofil, Endothel

Platelet, Fibroblast)

Delayed Inflammatory Response


9/38

PHYS

IOLOGIC

PAT

HOLOGI

C

Injury

Local Inflammatory

Restricted Systemic

Exaggerated Systemic

Sepsis / SIRS


10/38

Tahap-tahap SEPSIS / SIRS 1

Tahap I

Injury Sitokin proinflamasi mediator dan sel

melawan organisme patogen

Tahap II

Sebagian sitokin ke sirkulasi merekrut

makrofag dan platelet stimulasi growth factor

rapid inflammatory reaction.Sampai tahap II inifisiologik, dikendalikan oleh

sitokin anti inflamasi


11/38

Tahap-tahap SEPSIS / SIRS Tahap III

Clinical insult terlalu besar Sistem pengendalian tubuh tidak normal

homeostasis tak dapat dipertahankan

efek sitokin destruktif kerusakan organ yang

jauh dari infeksi MODS MOFS Perubahan yang terjadi

Progressive endhotelial dysfunctionspermeabilitas pembuluh darah meningkat.

Platelet sludging gangguan sirkulasi

maldistribusi aliran darah, iskemia dan reperfusioninjury

Aktivasi sistem koagulasi Vasodilatasi, transudasi cairan dan maldistribusi

aliran darahsyok


12/38

Tahap-tahap SEPSIS / SIRS

Tahap IV Terjadi kompensasi reaksi anti inflamasi yang

berlebihan imunosupresi / immune paralysis /CARS ( Compensated Anti inflammatory ResponseSyndrome)

CARS ditandai : Penurunan ekspresi HLA DR < 30% pada

permukaan monosit penurunan sekresi TNF danIL-6 anergi mudah terkena infeksi.

Tahap V

Tahap akhir dari MODS immunologic dissonance Penyebabnya :

Inflamasi yang berlebihan Depresi imun yang persisten


13/38

Pro-inflammatory

response

anti-inflammatory

response

CardiovascularCompromise

(shock)SIRS

Predominates

Homeostais

CARS andSIRS

Balanced

Apoptosis(cell death)

Death withminimal

inflammation

Organdysfunction

SIRSPredominates

Suppressionof the immune

systemCARS

Predominates

SystemicReaction

SIRS (pro-inflamma-tory)

CARS (antipro-inflamma-tory)

MARS(mixed)

Initial insult

(bacterial, viral, traumatic, thermal)

Systemic spillover of

pro-inflammatory

mediators

Systemic spillover of

anti-inflammatory

mediators


14/38

Treatment of Sepsis


15/38

SEVERE SEPSIS: EARLY RECOGNITION

SIRS Criteria:

Fever

Tachypnea

Tachycardia

Leukocytosis orleukopenia

Organ Failures:

Respiratory

paO2:FiO2 < 300

Cardiovascular

SBP < 90 mm Hg after IVF

RenalU/O < 30 mL/hr

CNS

Delirium

Metabolic

Lactate > 4 mmol/L, or anion gap

metabolic acidosis


16/38

HOMEOSTASIS IS LOST IN SEPSIS

PAI-1= plasminogen activator inhibitor-1;TAFIa= thrombin activatable fibrinolysis inhibitor. Carvalho and

Freeman. J Crit Illness. 1994;9:51; Kidokoro et al. Shock. 1996;5:223; Vervloet et al. Semin Thromb Hemost.1998;24:33.

Homeostasis

Proinflammatorymediators

Endothelial injury

Tissue factor expression

Thrombin production

Increased PAl-1

Increased TAFIa

Reduced Protein C(endogenous Activated

Protein C inhibits PAI-1)


17/38

SEVERE SEPSIS: A VICIOUS CYCLE OF INFLAMMATION AND

COAGULATION

Infection

Inflammation

Coagulation

Inflammation

Coagulation

Inflammation

Coagulation

EndothelialDysfunction

Ischemia

Organ Failure

Death

Inflammation

Esmon. Immunologist. 1998;6:84.


18/38

INTERVENTIONS IN SEVERE SEPSIS

What is harmful?

What doesnt work?What might / probably works?

What does work?


19/38

Initial Resuscitation

(first 6 hours)

Begin resuscitation immediately in patients withhypotension or elevated

serum lactate >4mmol/l; do not delay pending ICUadmission

Resusc i tation goals:

- Central venous pressure (CVP) 812 mm Hg*

-Mean arterial pressure 65 mm Hg-Urine output 0.5 mL.kg-1.hr-1

- Central venous (super ior vena cava) oxygensaturation 70%, or mixed venous 65%

If venous O2 saturat ion target no t ach ieved: con siderfurther f lu id

transfuse packed red blood cel ls i f required to hematocr i t of 30% and/or

dobutamineinfusion max 20 g.kg-1.min-1

* A higher target CVP of 12-15 mmHg is recommended in thepresence of mechanical ventilation or pre-existingdecreased ventricular compliance


20/38

Diagnosis

Obtain appropriate cultures before starting

antibiotics provided this does not significantlydelay antimicrobial administration

- Obtain two or m ore blood cu l tures(BCs)

- One or more BCs should be

percutaneous- One BC from each vascular accessdevice in place >48 hours

- Culture other sites as clinicallyindicated

Perform imaging studies promptly in order toconfirm and sample any source of infection; if safeto do so


21/38

Antibiotics

Begin intravenous antibiotics as early as possible,and always within the first hour of recognizingsevere sepsis and septic shock

Broad-spectrum: one or more agents activeagainst likely bacterial/fungal pathogens and withgood penetration into presumed source

Reassess antimicrobial regimen daily to optimizeefficacy, prevent resistance, avoid toxicity &

minimize costs


22/38

Antibiotics

Consider combination therapy in Pseudomonas

infections

Consider combination empiric therapy inneutropenic patients

Combination therapy no more than 3-5 days andde-escalation following susceptibilities

Duration of therapy typically limited to 710 days;longer if response slow, undrainable foci ofinfection, or immunologic deficiencies

Stop antimicrobial therapy if cause is found to benon-infectious


23/38

Source Infection and Control

A specific anatomic site of infection should beestablished as rapidly as possible and within the first 6hours of presentation

Formally evaluate patient for a focus of infectionamenable to source control measures (e.g. abscessdrainage, tissue debridement)

Implement source control measures as soon aspossible following successful initial resuscitation

Exception: infected pancreatic necrosis, where surgicalintervention best delayed

Choose source control measure with maximum efficacyand minimal physiologic upset

Remove intravascular access devices if potentiallyinfected


24/38

Fluid Therapy

Fluid-resusci tate us ing c rystal lo ids or col lo ids

Target a CVP of 8mmHg (12mmHg if mechanicallyventi lated)

Use a fluid challenge technique while associated witha hemodynamic improvement

Give fluid chal lenges of 1000 m l of crystal loids or300500 m l of co l loids over 30 m inu tes. More rapidand larger volumes may be required in sepsis-induced

t issue hypoperfus ion

Rate of fluid administration should be reduced if

cardiac filling pressures increase without concurrenthemodynamic improvement


25/38

Vasopressors

Maintain MAP 65mmHg

Norepinephr ine or dopamine centra lly adm inistered are

the ini t ial vasopresso rs of cho iceEpinephrine, phenylephrine or vasopressin should not beadministered as the initial vasopressor in septic shock

Vasopressin 0.03 units/min maybe subsequently addedto norepinephrine with anticipation of an effect

equivalent to norepinephrine aloneUse epinephrine as the first alternative agent in septicshock when :

- blood pressure is poorly responsive to norepinephrine ordopamine

- Do not use low-dose dopamine for renal protection- In patients requiring vasopressors, insert an arterial

catheter as soon as practical


26/38

Inotropic Therapy

Use dobu tam ine in pat ients withmyocard ial dysfunc t ion as suppor ted by

elevated cardiac fi l l ing p ressu res and low

cardiac outpu t

Do not increase cardiac index to

predetermined supra-normal levels


27/38

Steroids

Consider intravenous hydro cor t isone for adul t sept ic

shoc k when hypotension remains poo r ly responsive toadequate f lu id resusc i tat ion and vasop ressors

- ACTH stimulation test is not recommended to identifythe subset of adults with septic shock who shouldreceive hydrocortisone

- Hydrocortisone is preferred to dexamethasone

- Fludrocortisone (50 g orally once a day) may beincluded if an alternative to hydrocortisone is beingused which lacks significant mineralocorticoid activity

- Steroid therapy may be weaned once vasopressorsare no longer required

- Hydrocortisone dose should be


28/38

Recombinant Human Activated Protein C (rhAPC)

Consider rhAPC in adult patients with sepsis-

induced organ dysfunction with clinical assessment

of high risk of death (typically APACHE II 25 or

multiple organ failure) if there are no

contraindications

Adult patients with severe sepsis and low risk of

death (typically, APACHE II


29/38

Blood Product Administration

Give red b lood cel ls w hen hemog lob in decreases to


30/38

Mechanical Ventilation of Sepsis-induced

Acute Lung Injury (ALI)/ARDS

Target a t idal volum e of 6m l/kg (predicted) body w eight in pat ients w ith

ALI/ARDSTarget an initial upper limit plateau pressure 30cmH2O. Consider chestwall compliance when assessing plateau pressure

Allow PaCO2 to increase above normal, if needed to minimize plateaupressures and tidal volumes

Positive end expiratory pressure (PEEP) should be set to avoid extensive

lung collapse at end-expirationo Consider using the prone position for ARDS patients requiringpotentially injurious levels of FiO2 or plateau pressure, provided theyare not put at risk from positional changes

Maintain mechanic al ly vent i lated pat ients in a semi-recumbent (berbaring )pos i t ion unless c ontra indicated

Suggested t arget elevation 30 - 45 degrees

o Non invasive ventilation may be considered in the minority of ALI/ARDSpatients with mild-moderate hypoxemic respiratory failure. The patientsneed to be haemodynamically stable, comfortable, easily arousable,able to protect/clear their airway and expected to recover rapidly


31/38

Mechanical Ventilation of Sepsis-induced

Acute Lung Injury (ALI)/ARDS

Use a weaning protocol and a spontaneous breathing trial (SBT) regularly to

evaluate the potential for discontinuing mechanical ventilation

SBT options include a low level of pressure support with continuous positive

airway pressure 5 cm H2O or a T-piece.

Before the SBT, patients should:

Be arousableBe hemodynamically stable without vasopressors

Have no new potentially serious conditions

Have low ventilatory and end-expiratory pressure requirement

Require FiO2 levels that can be safely delivered with a face mask or nasal

cannula

Do not use a pulmonary artery catheter for the routine monitoring of patientswith ALI/ARDS

Use a conservative fluid strategy for patients with established ALI who do not

have evidence of tissue hypoperfusion


32/38

Sedation, Analgesia, and

Neuromuscular Blockade

Use sedat ion proto cols with a sedat ion goal for

cr i t ical ly i l l mechanical ly venti lated patients

Use either intermittent bolus sedation or continuous

infusion sedation to predetermined end points(sedation scales), with daily interruption/lightening to

produce awakening. Re-titrate if necessary

Avo id neuromuscular blockers where possib le.Monitor depth of block with train-of-four when using

continuous infusions


33/38

Glucose Control

Use IV insul in to contro l h yperg lycemia in pat ients wi thsevere sepsis fol low ing s tabi l izat ion in the ICU

Aim to keep blood gluc ose 150 mg/dL (


34/38

Renal Rep lacement

o Interm ittent haemod ialys is and

con t inuous veno-venous haemofi l t rat ion

(CVVH) are cons idered equ ivalent

o CVVH offers easier management in

hemodynamically unstable patients


35/38

Bicarbonate Therapy

Do no t use bicarbonate therapy fo r the

purpose of improv ing hemodynamics or

reducing vasop resso r requirements whentreat ing h ypoperfusion- induced lact ic

academia with pH 7.15


36/38

Deep Vein Thrombosis (DVT) Prophy laxis

Use either low -do se unfract io nated heparin(UFH) or low -molecular weight heparin(LMWH), un less cont ra-ind icated

Use a mechanical prophylactic device, such as

compression stockings or an intermittentcompression device, when heparin is contra -indicated

o Use a combination of pharmacologic andmechanical therapy for patients who are atvery high risk for DVT

o In patients at very high risk LMWH shouldbe used rather than UFH


37/38

Stress Ulcer Prophy laxis

Provide stress ulcer prophylaxis using H2

blocker or proton pump inhib i tor

Benefi ts of p revention o f upper GI bleedmus t be weighed against the potent ial for

developm ent of venti lator-associated

pneumonia


38/38

Consideration for Limitation of Support

Discuss advance care planning with patients

and families

Describe likely outcomes and set realisticexpectations

kuliah sepsis

Documents