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SEPSI

LEZIONI SEPSI E. I. 2003

SEPSIS HAS HIGH MORTALITY RATE EVEN WHEN THE INFECTING

ORGANISM IS KNOWN AND APPROPRIATE ANTIMICROBIAL

THERAPY USED.


Srun-Buiuon C Doyon F Carlet et al. Incidence, risk facrors, and outcome of severe sepsis and septic shock in adults. A multicenter prospecrive study in intensive care units. FrenchICU Group for Severe Sepsis. JAMA 1995; 274: 968—974.

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A RECENT SURVEY OF SEVERE SEPSIS IN THE USA ESTIMATED WHERE 751000 CASES EVERY YEAR, WITH A MORTALITY RATE OF 28,6%, WHICH INCREASED WITH AGE, FROM 10% IN CHILDREN TO 38,4% IN THOSE OVER 85 YR OLD. THE INCIDENCE RATE IS ALSO PROJECTED TO INCREASE BY 1.5% PER ANNUM.

Angus DC Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiolagy of severe sepsis in the UnitedSates: analysis of incidence, outcome, and associated costs

of care, Crit Care Med 2001; 29: 1303—13 10.LEZIONI SEPSI E. I. 2003

SEPSIS IS ASSOCIATED WITH PROLONGED STAY IN BOTH ICU

AND IN HOSPITAL

Sands KB, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. AcademìcMedical Center Consortiurn Sepsis Project Workìng Group.

JAMA 1997; 278: 234—240.






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…. A fact ….Trauma, surgery, infection &

otherdisturbance of micro- & macro-

physiology produce an earlyphysiological inflammatory

reaction


Sepsis: A Complex Disease

• This Venn diagram provides a conceptual framework to view the relationships between various components ofsepsis.

• The inflammatory changes of sepsis are tightly linked to disturbed hemostasis.

Adapted from: Bone RC et al. Chest. 1992;101:1644-55.Opal SM et al. Crit Care Med. 2000;28:S81-2.LEZIONI SEPSI E. I. 2003





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ONE HUNDRED YEARS AGO, EHRLICH AND METCHNIKOFF DESCRIBED TO SEPARATE SYSTEMS BY WHICH THE HOST FORESTALLS INFECTION.

THE PHAGOCYTES DISCOVERED BY METCHNIKOFF WHERE THE BULWARK OF A FORM OF PROTECTION THAT CAME TO BE KNOWN AS INNATE IMMUNITY .

THE ANTITOXINS (LATER ANTIBODIES) IDENTIFIED BY EHRLICH SUBSERVED THE FORM OF PROTECTION THAT ULTIMATELY WAS NAMED ADAPTIVE IMMUNITY AND WERE SOON FOUND TO BE REPRESENTED ONLY IN VERTEBRATES.



IN MAMMALS, ADAPTIVE AND INNATE IMMUNITY DEPENDE ON EACH OTHER IN

CERTAIN SPECIFIC WAYS





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The innate response is largely mediated by

white blood cells, such as neutrophils and

macrophages. These cells phagocytose and

kill the pathogens and contemporaneously

coordinate additional host responses by

eliciting the inflammatory response.






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Glycoprotein molecules known astoll-like receptors are found on the surface of various body defensecells. They are so named becausethey recognize and bind topathogen-associated molecularpatterns - molecular componentsassociated with microorganisms. These include bacterial molecules, there are also pattern-recognitionmolecules for viral and fungal cellwalls components. Binding of the microbial molecule to the toll-likereceptor sends a signal through the cytoplasm to the nucleus of the cellwhere it activates genes coding forthe synthesis and secretion of cytokines.






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LA MINACCIA E LO STIMOLO ALLA RISPOSTA DELL’ OSPITE PUO ESSERE IL

MICRORGANISMO INVASORE PER SE’ O SUOI VARI PRODOTTI CON LA STIMOLAZIONE DI UNA

SERIE DI EFFETTI QUALI IL RILASCIO DI CITOCHINE, LA PRODUZIONE DI

COMPLEMENTO, L’ ATTIVAZIONE DELLA COAGULAZIONE E DELL’ AGGREGAZIONE

PIASTRINICA






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The defense mechanisms include:

- the release of cytokines- the activation of neutrophils and monocytes- the activation of plasma protein cascade systems- the complement system- the intrinsic pathways of coagulation (contact system)

- extrinsic pathways of coagulation- the fibrinolytic system







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Inflammatory Overreactions

In some situations the innate system may overreact and continue to churn out peptides despite the fact that the invader has been fighted off and thus the acute

inflammatory response turns into a chronic one.


ACTIVATION AND RELEASE OF THESE MEDIATOR OCCUR IN THE TISSUES, AS WELL AS IN THE CIRCULATION.THE ENDOTELIUM IS THE LINING BETWEEN BLOOD AND TISSUES.(IN ADULT UMANS THE TOTAL SURFACE OF THIS CELL POPULATION HAS BEEN ESTIMATED TO BE > 1000 m2 )






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ENDOTHELIAL CELLS ARE NOT INERT CELLS. UNDER PHYSIOLOGIC CONDITIONS EXERT MANY FUNCTIONS:

These functions include prevention of coagulation, orchestration of the migration of blood cells into the tissues by expression of adhesion molecules,

production of chemoattractant compounds, regulation of the microcirculation by dictating the

tonus of the arterioles, regulation of blood pressure ( their effects on arterioles), and

regulation of vasopermeability.






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Under physiologic conditions, endothelial cells inhibit blood coagulation by various endothelial mechanisms:

a) They express thrombomodulin, which not only binds thrombin but also shifts the specificity of this clotting enzyme from fibrin to protein C ; activated protein C in the presence of its cofactor protein S catalytically inactivates activated factor V and VIII of the clotting system

b) They have proteoglycans, such as heparan sulfate, on their surface, which can bind and potentiate the inhibitors antithrombin III and tissue factor pathway inhibitor

c) they release low amounts of the plasminogen activator tissue-type plasminogen activator (tPA).

d) Inhibts platelet aggregation by producing prostacyclin and nitricoxide (NO)







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The Inflammatory endothelium

Upon stimulation by various cytokines, including interleukin IL-lα, IL-1β, and tumor necrosis factor

TNF-α, and also upon interaction with other inflammatory mediators, such as activated

complement, the functions of the endothelium may be grossly altered. Infact the endothelium

triggered by inflammatory stimuli loses its anticoagulant properties and becomes a

procoagulant surface.







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For many years, cellular injury has been seen

in black and white terms. A cell subjected to

minor damage usualIy recovers, whereas a

celI subjected to a more severe injury dies by

necrosis, but exist a morphologicalIy different

form of cell death termed apoptosis.







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Apoptosis, the programmed celI death, is a process by which celIs undergo inducible

non-necrotic cellular suicide. In contrast tonecrotic celI death, apoptosis depends on de

novo synthesis of proteins that initiate a cellular suicide program in response to

specific stimuli.Characteristic features of apoptosis include

chromatin condensation, membrane blebbing, and internucleosomal DNA framentation.


Apoptosis is, thus, a homeostatically-regulated process that normally occurs in healthy organisms to eliminate dysfunctional, infected, or excessive celIs.

The sepsis-induced dysregulation of apoptosis in organ tissue may result in organ dysfunction.

When the clearance capacity of phagocytosing cells is overwhelmed by the amount of apoptotic cells, secondary necrosis of apoptotic cells occurs, which may subsequently result in an inflammatory response






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TRE SONO GLI ASPETTI FONDAMENTALI IN CORSO DI INFIAMMAZIONE ED INFEZIONE:

1) IL MAGGIORE E’ QUELLO CIRCOLATORIO CON UNA SERIE DI ALTERAZIONI NON SOLO DEL CO, PA, SVR MA ANCHE DEL FLUSSO EMATICO A LIVELLODEL MICROCIRCOLO, DELLA DISTRIBUZIONE DEL FLUSSO EMATICO AGLI ORGANI E LE MODIFICAZIONI FISIOPATOLOGICHE INDOTTE DALL’ ALTERATO FLUSSO DISTRETTUALE (RENE, FEGATO, INTESTINO. CUORE, SISTEMA MUSCOLOSCHELETRICO, ENDROCRINO E LINFATICO )

2) SECONDO FATTORE PIU’ IMPORTANTE E’ QUELLO DELL’ INFIAMMAZIONE MEDIANTE IL SUO COMPLESSO SISTEMA DI MEDIATORI CHE AGISCONO SIA SULLA CELLULA CHE SULLA FUNZIONE DEGLI ORGANI

3) TERZO FATTORE E’ LA COMPLESSA INTERELAZIONE TRA MEDIATORI E CIRCOLAZIONE (COME I MEDIATORI INFLUENZANO L’ ENDOTELIO E LA MICROCIRCOLAZIONE E COME LA CIRCOLAZIONE INFLUENZA LA PRODUZIONE DEI MEDIATORI).





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Endothelium Vascularsmooth muscle

Endotoxin, infective organism

Endogenous mediators (TNF IL-1 IFN PAF Complement ,etc)

Endothelial cell activationSurface molecule expression

Endothelial cell damageInflammatory mediators

Maldistribution of blood flow

MOSF

Impaired regulation of tone:iNOSendothelial mediatedmyogenic,neural,metabolic

Vasodilation-vasopressorrefractory hypotension

Myocardialdepression

Leukocyte trafficking, activation, aggregation

Microvascular permeabilityTissue edema

Intravascular pooling

Platelet activation, adhesionand aggregation

altered red cell rheology

Altered coagualationMicrovascular thrombosis

DIC

Cellular Hypoxia

NO PGE2 PGI2ET-1 TXA2 ATII


IT IS NOW GENERALLY ACCEPTED THAT SEPSIS RESULTS FROM AN EXTENSIVE TRIGGERING OF THE

BODY’S DEFENSE MECHANISMS BY THE INVADING MICROORGANISMS

AND THEIR PRODUCTS.






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ACCP/SCCM Consensus Definitions

lSystemic Inflammatory Response Syndrome (SIRS)

–Systemic response to a variety of processes

Temperature >38°C < 36°C

HR > 90 bpm

RR > 20 or PaCO2 < 32mmHg

WBC > 12000 ml3 < 4000 ml3 or 10% immature cells

lSepsis–Infection plus

–≥2 SIRS criteria

lSevere Sepsis–Sepsis associated with hypotension ( < 90mmHg or 40% reduction of baseline)

–Organ dysfunction

lSeptic shock–Sepsis

–Hypotension despite fluid resuscitation

Bone RC et al. Chest. 1992;101:1644-55.






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Infezione

Batterica Fungina

Virale Parassitaria



MENTRE LE ATTIVITA’ E LE IDENTITA’ DI MOLTI DEI MEDIATORI DELLA SEPSI (ATTUALMENTE PIU DI

150 SEMBRANO ESSERE IMPLICATI) SONO STATE RELATIVAMENTE BEN STUDIATE E DEFINITE, LE MODALITA’ MEDIANTE LE QUALI VIENE INDOTTO

IL RILASCIO DI QUESTI MEDIATORI SOLO ORA COMINCIA A DIVENIRE CHIARO.





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PER ESEMPIO LA SEQUENZA DEGLI EVENTI PER GLI ORGANISMI GRAM NEGATIVI E’ CHE LA ENDOTOSSINA

(LPS) SI LEGA AD UNA SPECIFICA PROTEINA (LPB) NEL PLASMA FORMANDO UN NUOVO COMPLESSO

CHE SI LEGA AD UN RECETTORE DI MEMBRANA DEL MACROFAGO (CD 14) PER CUI SI HA L’ ATTIVAZIONE

DEL MACROFAGO CON RILASCIO DI CITOCHINE,IL RILASCIO DI MEDIATORI PROINFIAMMATORI

ATTRAE ULTERIORI MACROFAGI E MONOCITI E QUINDI IL CICLO SI RIPETE E SI ACCRESCE







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CITOCHINE PROINFIAMMATORIETNF – αQUESTA FAMIGLIA E’ COINVOLTA FORTEMENTE NEL REGOLARE LA PROLIFERAZIONE CELLULARE E L’ APOPTOSI. IL TNF – α HA ADDIZIONALI PROPRIETA’ PROINFIAMMATORIE RECLUTANDO ED ATTIVANDO NEUTROFILI, MACROFAGI E LINFOCITI E STIMOLANDO IL RILASCIO DI ALTRE CITOCHINE PROINFIAMMATORIE E PROTEINE DELLA FASE ACUTA.

IL – 1

IL – 6

IL – 8

GRAULOCITE – COLONY STIMULATING FACTOR





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CITOCHINE ANTIINFIAMMATORIE

IL – 10

TNF – receptors

IL – 1 ra

ALTRI MEDIATORI

• ATTIVAZIONE DEL SISTEMA COAGULATIVO• ATTIVAZIONE DEL COMPLEMENTO • CONTACT SYSTEM• PAF• METABOLITTI DELL’ ACIDO ARACHIDONICO• ROS (reactive oxygen species)• NO (nitric oxide)






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Severe Sepsis: Acute Organ Dysfunction and Disordered Hemostasis

• Severe Sepsis: Sepsis with signs of organ dysfunction in ≥1 of the following systems: – Cardiovascular– Renal– Respiratory– Hepatic– Hemostasis– CNS– Unexplained metabolic acidosis

Adapted from: Bone RC et al. Chest. 1992;101:1644-55. LEZIONI SEPSI E. I. 2003

Identifying Acute Organ Dysfunction as aMarker of Severe Sepsis

TachycardiaHypotension

↑ CVP↑ PAOP

Jaundice↑ Enzymes↓ Albumin

↑ PT

Altered Consciousness

ConfusionPsychosis

TachypneaPaO2 <70 mm Hg

SaO2 <90%PaO2/FiO2 ≤300

OliguriaAnuria

↑ Creatinine

↓ Platelets↑ PT/APTT↓ Protein C↑ D-dimer






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MOFIf the patient presents one or more of the following signs for more than 24 hours, during this day MOF is present :

Cardiac failure:HR < 54 bpm

MAP < 49 mmHg or Syst < 60 mmHg

VT or VF

pH serum < 7.24 or PaCO2 < 49 mmHg

Respiratory failure: RR < 5 min or > 49 min

PaCO2 50 mmHg

AaDO2 > 350 mmHg

Ventilator-dependence

Renal failure:Urine output < 479ml / 24h or 159ml / 8h

BUN serum >100microgr/100ml

Creatinine serum > 3.5 microgr/100ml

Hematological failure:WBC < 1000 cell/m3

Plt < 20000 cell/m3

Hct < 20 %

CNS failure:GCS < 6 (no sedation)



SOFA score ( SEPSIS – RELATED ORGAN FAILURE ASSESSMENT )

SOFA score 1 2 3 4

RESPIRATIONPaO2 / FiO2 (mmHg) ≤ 400 ≤ 300 ≤ 200 ≤ 100

COAGULATIONPLATELETS

≤ 150 ≤ 100 ≤ 50 ≤ 20

LIVERBILIRUBIN (mg/dl)

1,2 –1,9 2 - 5,9 6-11,9 ≥ 12

CARDIOVASCULARHYPOTENSION

SNCGCS

13 - 14 10 - 12 6 - 9 < 6

RENAL CREATININE mg/dl

1,2 – 1,9 2 – 3,4 3,5 – 4,9< 500 ml/die

>5,0< 220 ml/die

MAP<70 mmHg

DOPAMINE ≤ 5OR DOBUTAMUNE(ANY DOSE)

DOPAMINE ≥ 5OR EPINEPHRINE ≥ O,1NOREPINEPHRINE ≥ 0,1

DOPAMINE > 15EPINEPHRINE ≥ 0,1NOREPINEPHRINE ≥ 0,1

* ADRENERGIC AGENTS ADMINISTERED FOR AT LEAST 1 h ( doses given are in γ/Kg/min )





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INFECTION

ProinflammatoryMediators INFLAMMATION

Anti-inflammatoryMediators

Stimulates

Inhibits






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INFECTION

ProinflammatoryMediators INFLAMMATION


Stimulates

Inhibits

ENDOTHELIAL INJURY


Cascata della coagulazione






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INFECTION

ProinflammatoryMediators

INFLAMMATION


Stimulates

Inhibits

ENDOTHELIAL INJURY

COAGULATION

TF

T







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INFECTION


INFLAMMATION


Stimulates

Inhibits

ENDOTHELIAL INJURY

COAGULATION

TF

PAI-1

t-PA

FIBRINOLYSIS

TAFI

T


INFECTION


INFLAMMATION


Stimulates

Inhibits

ENDOTHELIAL INJURY

COAGULATION

TF

PAI-1

t-PA

FIBRINOLYSIS

TAFI

T TM Protein C

ActivatedProtein C

ActivatedProtein C

Activates LEZIONI SEPSI E. I. 2003





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Cytokines are an importantcomponent of the inflammation

response that characterisesacute lung iniury







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ALIAcute lung injury ( ALI ) is a distinct form of acute respiratory failure characterized by:

- diffuse pulmonary infiltrates- progressive hypoxemia- reduced lung compliance- normal hydrostatic pressure


Trauma doctors involved in treatingvictims of war had long been familiar

with this syndrome, called as whet lung, shock lung or Da-Nang lung.

In 1967 Ashbaugh published a case series in the Lancet which described

clinical syndrome termed:Adult Respiratory Distress Syndrom

( ARDS ) LEZIONI SEPSI E. I. 2003

ALI - ARDS





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Over the past 30 years, this syndrome has

came to be one of central problems of

intensive care: lung injury arising from a

variety of different etiologies but

characterised by bilateral infiltrates on x-ray,

hypoxemia and non cardiogenic edema


ALI - ARDS

ALI-ARDS DEFINITIONTHE TERM ACUTE LUNG INJURY HAS BEEN USED

AS AN UMBRELLA TERM FOR HYPOXEMIC RESPIRATORY FAILURE, A SEVERE VERSION OF WIHICH IS ARDS

The American-Eureopean Consensus Conference on ARDSAm.J.Respir.Crit.Care Med. 1994

- BILATERAL PULMONARY INFILTRATES ON CHEST X-RAY- PULMONARY CAPILLARY WEDGE PRESSURE <18mmHg- PaO2/FiO2 <300 =ALI- PaO2/FiO2 <200 = ARDS






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- SEPSIS- PNEUMONIA- MAJOR TRAUMA- PULMONARY APIRATION AND NEAR DROWNING- BURNS- INHALATION OF NOXIOUS FUMES- FAT EMBOLISM- MASSIVE BLOOD TRASFUSION- AMNIOTIC FLUID EMBOLISM- AIR EMBOLISM- ECLAMPSIA- POISONING- RADIATION

CAUSES OF ALI - ARDS






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• ALI is most often sean as part of systemicinflammatory process, particularly systemicsepsis, where the lung manifestations parallelthose of rhe other tissues.

• Widespread destruction of the capillaryendothelium, extravasation of protein rich fluidand interstitial edema.

• In addition the alveolar basement membrane isdamaged and fluid seeps into the airspaces, stiffering the lungs and causing ventilation-perfusion mismatch.

ALI - ARDS


ALI - PATHOLOGY

THERE ARE TWO MAJOR STAGES:

- THE ACUTE PHASE CHARACTERIZED BY DISRUPTION

OF THE ALVEOLAR –CAPILLARY INTERFACE, LEAKAGE

OF PROTEIN RICH FLUID INTO THE INTERSITIUM AND

ALVEOLAR SPACE AND EXTENSIVE RELEASE OF

CYTOKINES AND MIGRATION OF NEUTROPHILS






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ALI- PATHOLOGY

• A LATER REPARATIVE PHASE IS CHARACTERIZED BY FIBRIPROLIFERATION AND ORGANIZATION OF LUNG TISSUE.

IF RESOLUTION NOT OCCUR DISORDERED COLLAGEN DEPOSITION OCCURS LEADING TO EXTENSIVE LUNG SEARRING.






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ARDS


ARDS Classic Chest X Ray of a patient with ARDS, although the lung injury appears diffuse, when you look at the CT scan of the same patient on the right you can see that the lower lobes are densely consolidated and the upper lobes relatively spared.






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A = establish an patient airway, intubate as necessary.

B = mec. vent. and obtain an adequate M. V. to maintain O2 delivery.

C = B.D., intravasc. bol. – fluid resusc and vasopressors as necessary

D = find the underlying problem and control the source

E = empiric therapy, for example antimicrobials for sepsis

FG = feed the Gut, to prevent villus atrophy and bacterial translocation

Management of patients with respiratory failure

1. Give enough oxygen to keep the PaO2 over 60 mmHg preferably, and over 50mmHg at the very least.

2. Avoid volotrauma and barotrauma, by keeping the tidal volumes in the 4-6ml/kg range and the airway plateau pressure below 30 - 35cmH2O (the tidal volume should not be less than 4ml/kg, irrespective of airway pressure).

The PaO2 is a function of the FiO2, the PEEP level, the mean airway pressure and the minute ventilation.

The principles of mechanical ventilation :





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PROLONGED INFLAMMATION AND DESTRUCTION OF PNEUMOCYTES LEADS TO FIBROBLASTIC PROLIFERATION , HYALIN MEMBRANE FORMATION AND LUNG FIBROSIS. EXTENSIVE MICROVASCULAR THROMBOSIS MAY LEAD TO PULMONARY HYPERTENSION, MYOCARDIAL DISFUNCTION AND SYSTEMIC HYPOTENSION.

SOME PATIENTS RAPIDLY RECOVERY FROM ACUTE LUNG INJURY AND HAVE NO PERMANENT SEQUELAE.

ALI- PATHOLOGY



CIRCA LA PATOGENESI DELLO SHOCK SETTICO VI SONO ORMAI EVIDENZE SCIENTIFICHE CHE LA STESSA RISPOSTA INFIAMMATORIA DELL’ OSPITE E’ IN LARGA PARTE RESPONSABILE DELLA SUA INSORGENZA

INFATTI A CERTI “ LIVELLI NORMALI “ IL RILASCIO DI QUESTI MEDIATORI DELLA RISPOSTA INFIAMMATORIA HA UN RUOLO PROTETTIVO NELLA REGOLAZIONE DELLA STESSA MA DURANTE UNA INFEZIONE SEVERA LA “ SUPERPRODUZIONE ” PUO’ PORTARE A MODS, MOF E MORTE IN TEMPI CHE VANNO DA ORE A QUALCHE GIORNO

SHOCK SETTICO





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LO SHOCK SETTICO E’ UNA SINDROME GRAVISSIMA CON RISCHIO PER LA VITA INDOTTA DA MICRORGANISMI, DALLE LORO TOSSINE O DA ENTRAMBI CHE HANNO INVASO IL CIRCOLO EMATICO DELL’ OSPITE

EMOCOLTURE SIA DI GERMI GRAM POSITIVI CHE NEGATIVI SONO COMUNEMENTE POSSIBILI ANCHE SE UNA VARIETA’ DI MICRORGANISMI QUALI FUNGHI, PROTOZOI E VIRUS POSSONO INDURRE SHOCK SETTICO

SHOCK SETTICO

LO SHOCK SETTICO RAPPRESENTA DAL PUNTO DI VISTA METABOLICO UNO

SQUILIBRIO TRA LA DOMANDA DI OSSIGENO ED IL POSSIBILE TRASPORTO E PERTANTO E’ UNO SHOCK DI TIPO DISTRIBUTIVO SEBBENE

LE COMPONENTI CARDIOGENA ED IPOVOLEMICA POSSANO ESSERE COINVOLTE.

SHOCK SETTICO






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E’ CLASSICAMENTE ASSOCIATO AD UN’ INCREMENTO DELL’ ACIDO LATTICO, AD UNA GITTATA CARDIACA NORMALE O AUMENTATA ED A RESISTENZE VASCOLARI PERIFERICHE

DIMINUITE.LE ALTERAZIONI DELLA PERMEABILITA’

CAPILLARE INDUCONO EDEMA CON FORMAZIONE DI UN TERZO SPAZIO ED

ALTERATA FUNZIONE TISSUTALE

SHOCK SETTICO



LO SHOCK SETTICO E’ UN INSUFFICIENZA CIRCOLATORIA ACUTA IN CORSO DI SEPSI SEVERA E RAPPRESENTA IL RISULTATO FINALE DELLA INTEREAZIONE TRA MICRORGANISMI E LORO PRODOTTI ED I FATTORI RILASCIATI DALL’ OSPITE IN RISPOSTA ALL’ INVASIONE.

QUESTA RISPOSTA E’ UN MECCANISMO INNATO SVILUPPATO PER PROTEGGERE L’ ORGANISMO MA SE STIMOLATO IN ECCESSO PUO DETERMINARE EFFETTI CATASTROFICI QUALI LA MODS, MOF E LA MORTE.

SHOCK SETTICO





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STRATEGIE POSSIBILI NELLA GESTIONE DEI PAZIENTI SETTICI

• VELOCE INDIVIDUAZIONE DEI PAZIENTI E DIAGNOSI

• RICONOSCIMENTO DELL’ ORGANISMO CAUSANTE IN TEMPI BREVI

• TERAPIA ANTIMICROBICA APPROPRIATA E TEMPESTIVA

• TECNICHE DI SOSTEGNO VENTILATORIE

• SUPPORTO EMODINAMICO APPROPRIATO

• TERAPIA FARMACOLOGICA MIRATA (PROTEINA C RICOMBINANTE ATTIVATA )

• TERAPIA IMMUNOLOGICA (IDROCORTISONE – FLUOROCORTISONE)

• CONTROLLO GLICEMICO (TERAPIA INSULINICA INTENSIVA)

• NUTRIZIONE APPROPRIATA

• TERAPIE DI SUPPORTO EFFICACI ( ULCERA DA STRESS, DIALISI, ETC.)

• GESTIONE DA PARTE DI STAFF MEDICO – INFERMIERISTICO QUALIFICATO


DIAGNOSI

Laboratorio • EMOCROMO• EMOGASANALISI• ACIDO LATTICO• ELETTROLITI• FUNZIONE RENALE• ENZIMI EPATICI• COAGULAZIONE•ESAME COLTURALE PRE ANTIBIOTICI: SANGUE, URINE,SECRETO BRONCHIALE, SE NECESSARIO LIQUIDO CEFALO – RACHIDIANO, PLEURICO O PERITONEALE





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DIAGNOSI

STRUMENTALE

• RADIOLOGICA

• ECOGRAFICA


MONITORAGGIO

• PRESSIONE ARTERIOSA INVASIVA

• CATETERIZZAZIONE ARTERIA POLMONARE

• TEMPERATURA

• DIURESI





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TRATTAMENTO

FLUIDOTERAPIA

INCREMENTARE VALORI PRESSORI E PERFUSIONE D’ ORGANO IL PIU’ RAPIDAMENTE POSSIBILE

• CRISTALLOIDI

• COLLOIDI

• EMODERIVATI


TRATTAMENTOAGENTI VASOATTIVI

OBIETTIVO PRIMARIO E’ NORMALIZZARE LA PERFUSIONE TISSUTALE INCREMENTANDO LA

PRESSIONE ARTERIOSA E QUANDO NECESSARIO LA CONTRATTILITA’ MIOCARDICA E QUINDI IL

TRASPORTO DI OSSIGENO





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FARMACO

α 1

DOPAMINA*

NORADRENALINA

DOBUTAMINA

ATTIVITA’ SUI RECETTORI

β1 DOPAMINERGICO

2+

3+

½+

2/3+

3+

2+

3+

3+

β2

2+

?

2+

3+

3+

0

0

0ADRENALINA*

AGENTI VASOATTIVI

*L’ ATTIVITA’ E’ DOSE DIPENDENTE


Drug Clinical effect Usual Dose Range

Epinephrine α and β adrenergic agonist

Norepinephrine

Dopamine

Dobutamine

Pharmacologic role

α and β adrenergic agonist*

Dopamine and β adrenergic agonist,progressive α – adrenergic effect with increasing doses

β adrenergic agonist

Chronotropism, inotropism,vasoconstriction

Chronotropism, inotropism,vasocostriction

Chronotropism, inotropism,vasoconstriction

Chronotropism, inotropism,vasocostriction

5 to 20 μg/min

5 to 20 μg/min

2 to 20 μg/Kg/min

5 to 15 μg/Kg/min

DRUGS COMMONLY USED FOR CIRCULATORY SUPPORT

* The α adrenergic effect is greater than the β adrenergic effect





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FARMACO DOSE

DOPAMINA*

NORADRENALINA

DOBUTAMINA

EFFETTO

CO

5 – 20γ/Kg/min

0.05 – 5 γ/Kg/min

2+

-/0/+

2+

2+

MAP

1+

2+

-/0/+

2+

1+

2+

-

2+ADRENALINA*

SVR

5 – 20 γ/Kg/min

0.05 – 2 γ/Kg/min

*L’ ATTIVITA’ E’ DOSE DIPENDENTE

AGENTI VASOATTIVI


TRATTAMENTO

Antibiotici

• SCELTA APPROPRIATA E TEMPESTIVA

• STATO IMMUNITARIO DELL’ OSPITE





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DO2 / VO2

L’ ACIDOSI LATTICA RAPPRESENTA LO SQUILIBRIO TRA CONSUMO E TRASPORTO DI OSSIGENO LE CAUSE POTENZIALI INCLUDONO:

• INADEGUATO DO2

• INCREMENTO VO2

• INCAPACITA’ DEI TESSUTI AD UTILIZZARE L’ OSSIGENO

IL TRASPORTO DI O2 PUO’ ESSERE OTTIMIZZATO PORTANDO LA SaO2 > 90%, L’ Hb > 8 g/dl E INCREMENTANDO IL CI A VALORI TRA 4.5 – 6 l/min/m2

IL CONSUMO DI OSSIGENO PUO’ ESSERE RIDOTTO CON IL CONTROLLO DELLA TEMPERATURA E CON, SE E’ DETERMINANTE IL LAVORO RESPIRATORIO, VENTILAZIONE MECCANICA PREVIA SEDAZIONE E PARALISI

.


ALTRE TERAPIE

• CORTICOSTEROIDI

• BICARBONATO

• INIBITORI DELLA SINTESI DELL’ OSSIDO NITRICO

• NALOXONE

• INIBITORI DEI MEDIATORI

• CRRT

• PROTEINA C ATTIVATA RICOMBINANTE





48


EFFICACIA DI BASSE DOSI DI STEROIDI NELLO SHOCK SETTICO

•100mg di idrocortisone tre volte al giorno per 5 ggBollaert PE, Charpentier C, Levy 5 et al. Reversal of septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 1998; 26: 645 - 50

• 100 mg di idrocortisone seguite da 0,18 mg/Kg/h per 5–10 ggBriegel J,Forst H,Haller M et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: A prospective, randomized, double-blind, singie center study. Crit Care Med 1999;27:723—32.

• 50 mg di idrocortisone ogni 5 h i.v. + 50 mg di fluorocortisoneper via enterale per 5 gg.

Annane D et al. Effects of the combination of hydrocortisone (HC) and fluorocortisone (FC) on mortality in septic shock. Crit Care Med 2000;28:A46 (Abstract 63).

Homeostasis Is Unbalanced in Severe Sepsis

Carvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock.1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44. LEZIONI SEPSI E. I. 2003





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In patients with severe sepsis an intravenous infusion of drotecogin alfa ( 24 micrograms/kg per hour for 96 h) activatedsignificantly reduces mortality. Treatment may be associatedwith an increased risk of bleeding





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