SEPSISSEPSIS

SEVERE SEVERE SEPSISSEPSIS

SEPTIC SHOCKSEPTIC SHOCK

Rontgene M. Solante,M.D.,FPCP,FPSMIDRontgene M. Solante,M.D.,FPCP,FPSMID Internal Medicine – Infectious DiseasesInternal Medicine – Infectious Diseases

SEPSIS: WHAT DO WE KNOW?SEPSIS: WHAT DO WE KNOW? Sepsis (Greek): “rotten flesh and putrefaction”Sepsis (Greek): “rotten flesh and putrefaction”

““complex medical condition that begins with an complex medical condition that begins with an infectious stimulus and results in an infectious stimulus and results in an exaggerated immune response”exaggerated immune response”

European Study: >35% of patients develop European Study: >35% of patients develop sepsis at some point during their ICU stay; 30% sepsis at some point during their ICU stay; 30% severe sepsis; mortality- 27% sepsis and >50% severe sepsis; mortality- 27% sepsis and >50% if septic shockif septic shock

- Jean-Louis Vincent, et al. Sepsis in European Intensive Care Units: Results of SOAP Study. 2006- Jean-Louis Vincent, et al. Sepsis in European Intensive Care Units: Results of SOAP Study. 2006

Sepsis: A Complex DiseaseSepsis: A Complex Disease

This Venn diagram This Venn diagram provides a conceptual provides a conceptual framework to view framework to view the relationships the relationships between various between various components components of sepsis. of sepsis.

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

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

Sepsis: ACCP/SCCM DefinitionsSepsis: ACCP/SCCM Definitions

InfectionInfection– Inflammatory response to microorganisms, orInflammatory response to microorganisms, or– Invasion of normally sterile tissues Invasion of normally sterile tissues

Systematic Inflammatory Response Syndrome(SIRS)Systematic Inflammatory Response Syndrome(SIRS) > > 2 of the following:2 of the following:– Core temperature >38Core temperature >38oo C or <36 C or <36ooC (>100.4C (>100.4oo F or <96.8 F or <96.8oo F) F)– Elevated heart rate (>90 beats/min)Elevated heart rate (>90 beats/min)

– Respiratory rate >20 breaths/min or PACORespiratory rate >20 breaths/min or PACO22 <32 mm Hg <32 mm Hg

or mechanical ventilation for acute respiratory processor mechanical ventilation for acute respiratory process

– WBC count > 12,000 cells/mmWBC count > 12,000 cells/mm3 3 or <4,000 cells/mmor <4,000 cells/mm33 or or

>10%>10% immature neutrophils immature neutrophils

Sepsis: ACCP/SCCM Sepsis: ACCP/SCCM Definitions Definitions

Known or suspected infection, Known or suspected infection, plusplus>>2 SIRS criteria:2 SIRS criteria:– Core temperature >38Core temperature >38oo C or <36 C or <36ooC (>100.4C (>100.4oo F F

or <96.8or <96.8oo F) F)– Elevated heart rate (>90 beats/min)Elevated heart rate (>90 beats/min)

– Respiratory rate >20 breaths/min or PACORespiratory rate >20 breaths/min or PACO22 <32 mm Hg or mechanical ventilation for <32 mm Hg or mechanical ventilation for acute respiratory processacute respiratory process

– WBC count > 12,000 cells/mmWBC count > 12,000 cells/mm3 3 or <4,000 or <4,000

cells/mmcells/mm33 or >10% immature neutrophils or >10% immature neutrophils

Severe Sepsis: Acute Organ Severe Sepsis: Acute Organ Dysfunction and Disordered Dysfunction and Disordered

HemostasisHemostasis Severe Sepsis: Severe Sepsis:

Sepsis with signs of Sepsis with signs of organ dysfunction in organ dysfunction in 1 1 of the following of the following systems: systems: – CardiovascularCardiovascular– RenalRenal– RespiratoryRespiratory– HepaticHepatic– HemostasisHemostasis– CNSCNS– Unexplained metabolic Unexplained metabolic

acidosisacidosis

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

Severe Sepsis (Sepsis syndrome)1. Cardiovascular:

Arterial systolic BP< 90 mmHg or mean arterial pressure (MAP) <70 mmHg that responds to administration of fluid2. Renal:

Urine output < 0.5 ml/kg per hour for 1 hr despite adequate fluid resuscitation3. Respiratory:

PaO2 /FiO2 <250 or, if the lung is the only dysfunctional organ, <2004. Hematologic:

Platelet count <80,000/uL or 50% decrease in platelet count from highest value recorded over previous 3 days

Septic Shock

-Sepsis with hypotension despite adequate fluid resuscitation accompanied by perfusion abnormalities

SEPSISSystemic response to infection with

Same manifestation as SIRS

BACTEREMIAThe presence of livebacteria in the blood

INFECTIONInflammatory response to

the presence of or invasionof normally sterile host

tissue by microorganisms

SEVERE SEPSISSepsis associated with organ dysfunction, hypopefusion or hypotension. Perfusion abnormalities may include but are not limited to:• Lactic acidosis• Oliguria• Acute mental status changes

SEPTIC SHOCKSepsis with hypotension despite adequate

fluid resuscitation accompanied byperfusion abnormalities

HYPOTENSIONSystolic BP < 90 or↓ from baseline> 40 mmHg

2º MODSAltered organ functionin acutely ill patientrequiring intervention

Systemic Inflammatory Response Syndrome (SIRS)

Severe Sepsis: A Complex and Severe Sepsis: A Complex and Unpredictable Clinical Unpredictable Clinical

SyndromeSyndrome Sepsis-induced organ Sepsis-induced organ failure:failure:

-? Cause (autopsies): -? Cause (autopsies): discordant findingsdiscordant findings

- tissue hypoxia (microvascular - tissue hypoxia (microvascular blood flow studies in mucosal blood flow studies in mucosal membranes)membranes)

Alterations in cell Alterations in cell metabolisms- oxidative metabolisms- oxidative modifications of proteins, modifications of proteins, lipids, DNAslipids, DNAs

- Vincent JL and Abraham E. The Last 100 Years of Sepsis- Vincent JL and Abraham E. The Last 100 Years of Sepsis. AJRCCM . AJRCCM 2006; 173:256-63.2006; 173:256-63.

ACUTE ORGAN ACUTE ORGAN DYSFUNCTIONDYSFUNCTION(Severe Sepsis)(Severe Sepsis)

DEATHDEATH

SEPSISSEPSIS

PATHOPHYSIOLOGY:PATHOPHYSIOLOGY:Microcirculatory dysfunctionMicrocirculatory dysfunction

Cytopathic hypoxia Cytopathic hypoxia ––diminished production of ATP diminished production of ATP despite normal PO2 values in the vicinity of despite normal PO2 values in the vicinity of

mitochondria within cellsmitochondria within cells↓↓

Activation or Injury of the vascular endotheliumActivation or Injury of the vascular endotheliumSecondary to alteration of vascular tone, vascular Secondary to alteration of vascular tone, vascular

permeability and coagulationpermeability and coagulation↓↓

↓↓Activation of cytokines and other mediatorsActivation of cytokines and other mediators

↓↓Complement ActivationComplement Activation

↓↓CoagulopathyCoagulopathy

↓↓ImmunosuppressionImmunosuppression

Microorganisms Involved in Episodes of Microorganisms Involved in Episodes of Severe Sepsis Severe Sepsis

Episodes with Episodes with Episodes withEpisodes with Total Episodes, Total Episodes,

bloodstream bloodstream DocumentedDocumented %%

infection, %infection, % Infection But NoInfection But No (n= 866) (n= 866)

(n=436)(n=436) Bloodstream Bloodstream

infection, %infection, %

(n= 430)(n= 430)

Gram negative bacteriaGram negative bacteria 35 35 44 44 40 40

Gram positive bacteriaGram positive bacteria 40 40 24 24 31 31

FungiFungi 7 7 5 5 6 6

PolymicrobialPolymicrobial 11 11 21 16 21 16

Classic PathogensClassic Pathogens <5 <5 <5 <5 <5 <5

Proinflammatorycytokine, coagulation system,

neutrophil activation

AntiinflammatoryCytokine, natural inhibitor release,

Stress hormones, immune cell activation

Fulminant SIRSEarly Mortality

Excessive Response Excessive Response

ImmunoparalysisLate Mortality

Outcome

Balance between proinflammatory and counter-regulatoryevents in response to infection determines clinical outcome

Normal Host Responses to InfectionNormal Host Responses to Infection

Local Defenses: Walling Off and Killing Invading MicrobesLocal Defenses: Walling Off and Killing Invading Microbes Systemic Responses: Keeping Infection and Inflammation localizedSystemic Responses: Keeping Infection and Inflammation localized

a.) CNS Regulation of Systemic Responsea.) CNS Regulation of Systemic Responseb.) Essential Roles of Liver and Spleenb.) Essential Roles of Liver and Spleen

Acute Phase ResponsesAcute Phase Responsesa.) Anti-infective Responsesa.) Anti-infective Responsesb.) Anti-inflamatory responsesb.) Anti-inflamatory responsesc.) Metabolic responsesc.) Metabolic responsesd.) Procoagulant responsesd.) Procoagulant responsese.) Thermoregulatory Responsese.) Thermoregulatory Responses

Walling off and Killing Invading Walling off and Killing Invading MicrobesMicrobes

Innate ImmunityInnate Immunity Senses microbes through proteins that bring Senses microbes through proteins that bring

highly conserved microbial molecules highly conserved microbial molecules (lipopolysaccharides, peptiglycan)(lipopolysaccharides, peptiglycan)

““Hard-wired” –inferited in the genome; shaped Hard-wired” –inferited in the genome; shaped by evolutionby evolution

Responds rapidly to microbial invasionResponds rapidly to microbial invasion ElementsElements: mannose-binding-lectin, alternative : mannose-binding-lectin, alternative

complement pathway, “natural” antibodies, complement pathway, “natural” antibodies, pattern – recognition proteins, the “professional” pattern – recognition proteins, the “professional” phagocytes, mast cells, (NK) natural killer cellsphagocytes, mast cells, (NK) natural killer cells

Systemic Responses: Keeping Infection Systemic Responses: Keeping Infection and Inflammation localizedand Inflammation localized

a.) a.) CNS Regulation of Systemic ResponseCNS Regulation of Systemic ResponseThe CNS senses microbial invasion via:The CNS senses microbial invasion via:

1.1. afferent impulses along nociceptive and vagal nerves afferent impulses along nociceptive and vagal nerves rapidly transmit signals from infected local tissues to rapidly transmit signals from infected local tissues to the hypothalamus and brainstem where they can the hypothalamus and brainstem where they can activate the hypothalamic-pituitary-adrenal (HPA) axisactivate the hypothalamic-pituitary-adrenal (HPA) axis, , the autonomic nervous systemthe autonomic nervous system and and the hypothalamic the hypothalamic thermoregulatory centerthermoregulatory center

2.2. Blood-borne mediators (IL-IBlood-borne mediators (IL-Iββ, TNF, IL-6, interferons , TNF, IL-6, interferons and prostaglandins) can cross the blood-brain barrier and prostaglandins) can cross the blood-brain barrier or be transported passively through capillaries in the or be transported passively through capillaries in the circumventricular organs to reach the hypothalamuscircumventricular organs to reach the hypothalamus

Systemic Responses: Keeping Systemic Responses: Keeping Infection and Inflammation Infection and Inflammation

localizedlocalized Role of Liver and SpleenRole of Liver and Spleen

The liver acts as a The liver acts as a blood filter that collects and blood filter that collects and kills blood-borne microbes,kills blood-borne microbes, as a “listening station” that as a “listening station” that senses low concentration of circulating cytokines and senses low concentration of circulating cytokines and transmits this information to the CNS, as a factory for the transmits this information to the CNS, as a factory for the production of many elements of the systemic response, production of many elements of the systemic response, and as a major site of infection-associated metabolic and as a major site of infection-associated metabolic adaptations.adaptations.

The spleen functions as The spleen functions as the major filter for the major filter for opsonized microorganisms. opsonized microorganisms.

Acute Phase ResponsesAcute Phase Responses

A.A. Anti-infective responsesAnti-infective responses

- - increases synthesis of complement factors, increases synthesis of complement factors, microbe pattern-recognition molecules (mannose-microbe pattern-recognition molecules (mannose-binding lectin, LBP, CRP, CD14 and others)binding lectin, LBP, CRP, CD14 and others)

- sequesters iron (lactoferrin) and zinc - sequesters iron (lactoferrin) and zinc (metallothionein)(metallothionein)

B.B. Anti-inflammatory ResponsesAnti-inflammatory Responses- releases anti-inflammatory neuroendocrine - releases anti-inflammatory neuroendocrine hormones (cortisol, ACTH, epinephrine, hormones (cortisol, ACTH, epinephrine, MSH)MSH)- increases synthesis of proteins that help - increases synthesis of proteins that help prevent inflammation within the systemic prevent inflammation within the systemic compartmentcompartment

. Cytokinase antagonists (IL-1Ra). Cytokinase antagonists (IL-1Ra)

. Anti-inflammatory mediators. Anti-inflammatory mediators

. Protease inhibitors. Protease inhibitors

. Antioxidants. Antioxidants - reprograms circulating leukocytes - reprograms circulating leukocytes (epinephrine, cortisol, PGE)(epinephrine, cortisol, PGE)

C.C. Metabolic ResponsesMetabolic Responses- preserves euglycemia, mobilizes fatty acids, - preserves euglycemia, mobilizes fatty acids,

epinephrine, cortisol, glucagon, cytokinesepinephrine, cortisol, glucagon, cytokines

D.D. Procoagulant ResponsesProcoagulant Responses- walls off infection, prevents systemic spread - walls off infection, prevents systemic spread

by:by:. increasing synthesis or release of . increasing synthesis or release of fibrinogen, PAI-I, C4bfibrinogen, PAI-I, C4b. decreasing synthesis of protein C, anti-. decreasing synthesis of protein C, anti-thrombin IIIthrombin III

E.E. Thermoregulatory ResponsesThermoregulatory ResponsesInhibits microbial growth (fever)Inhibits microbial growth (fever)

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

Identifying Acute Organ Identifying Acute Organ Dysfunction as a Marker of Severe Dysfunction as a Marker of Severe

SepsisSepsis

TachycardiaTachycardiaHypotensionHypotension

CVPCVP PAOPPAOP

JaundiceJaundice EnzymesEnzymes AlbuminAlbumin

PTPT

Altered Altered ConsciousnesConsciousnes

ssConfusionConfusionPsychosisPsychosis

TachypneaTachypneaPaOPaO22 <70 mm Hg <70 mm Hg

SaOSaO22 <90% <90%PaOPaO22/FiO/FiO22 300 300

OliguriaOliguriaAnuriaAnuria

CreatinineCreatinine

PlateletsPlatelets PT/APTTPT/APTT Protein CProtein C D-dimerD-dimer

Nervous and Neuroendocrine Nervous and Neuroendocrine SystemsSystems

a.a. Cerebral function Cerebral function

- confusion and other subtle - confusion and other subtle

abnormalities in cognitive abnormalities in cognitive

functionfunction

- focal signs, seizures and - focal signs, seizures and

cranial nerve palsies cranial nerve palsies

- encephalopathy is - encephalopathy is

associated with poorassociated with poor

prognosisprognosis

b.b. Hypothalamic-Pituitary-Adrenal axisHypothalamic-Pituitary-Adrenal axis

high plasma concentration of vasopressin are high plasma concentration of vasopressin are followed by relatively low levels, probably followed by relatively low levels, probably reflecting both loss of baroreflex feedback reflecting both loss of baroreflex feedback regulation and vasopressin depletion from the regulation and vasopressin depletion from the posterior pituitaryposterior pituitary

c.c. Adrenal InsufficiencyAdrenal Insufficiency

-- due to anatomic damage to the adrenals due to anatomic damage to the adrenals or pituitary, hypoperfusion, cytokine-induced or pituitary, hypoperfusion, cytokine-induced dysfunction of adrenals, drug induced steroid dysfunction of adrenals, drug induced steroid hypermetabolism, inhibitionof hypermetabolism, inhibitionof steroidogenesis and desensitization to steroidogenesis and desensitization to glucocorticoid responsiveness at the cellular glucocorticoid responsiveness at the cellular levellevel

- manifested as - manifested as hypotensionhypotension and and hypoglycemiahypoglycemia

d.d. Autonomic dysfunctionAutonomic dysfunction

manifested as oscillations in heart rate, blood manifested as oscillations in heart rate, blood pressure, respiration pressure, respiration

e.e. Peripheral Nerves, MusclesPeripheral Nerves, Muscles

polyneuropathy and myopathy manifested as polyneuropathy and myopathy manifested as difficulty in weaning from ventilator, difficulty in weaning from ventilator, generalized wasting of limbs and diffuse generalized wasting of limbs and diffuse weaknessweakness

THE BLOOD STREAMTHE BLOOD STREAM

A.A. The HeartThe Heart

- - reduced left and reduced left and

right ventricular right ventricular

ejection fractionsejection fractions

-- increased left and increased left and

right ventricular right ventricular

end-end- diastolic volumediastolic volume

- elevated heart rate and - elevated heart rate and

cardiac outputcardiac output

SEPTIC SHOCKSEPTIC SHOCK

Phases of septic shock:Phases of septic shock:

1.1. Vasoconstrictive (cold) shockVasoconstrictive (cold) shock

low cardiac outputlow cardiac output and and high peripheral high peripheral resistanceresistance in hypovolemic pts. secondary to in hypovolemic pts. secondary to redistribution of blood flow, venous pooling, redistribution of blood flow, venous pooling, increased capillary permeability, increased increased capillary permeability, increased insensible losses and poor fluid intakeinsensible losses and poor fluid intake

2.2. VasodilationVasodilation

Clinical hallmarksClinical hallmarks::

decreased systemic vascular decreased systemic vascular resistanceresistance

high cardiac output.high cardiac output.

LipidsLipids

- - decrease in levels of HDL and LDLdecrease in levels of HDL and LDL

- increase in levels of triglycerides, free - increase in levels of triglycerides, free fatty fatty acids and VLDLacids and VLDL

GlucoseGlucose

- - hypoglycemia is uncommon since the body hypoglycemia is uncommon since the body can maintain glucose levels through can maintain glucose levels through gluconeogenesisgluconeogenesis, , glycogenolysisglycogenolysis and and insulin insulin resistanceresistance

LactateLactate

- increased blood lactate concentrations and - increased blood lactate concentrations and increased lactate to pyruvate ratio due increased lactate to pyruvate ratio due impaired hepatic lactate clearance and impaired hepatic lactate clearance and mitochondrial dysfunctionmitochondrial dysfunction

Coagulopathy / DICCoagulopathy / DIC

diagnostic criteria for DIC:diagnostic criteria for DIC:1. platelet count <100,000/mm1. platelet count <100,000/mm33 or rapid or rapid

decrease in platelet count;decrease in platelet count;

Acute Lung InjuryAcute Lung Injury

Hyperventilation with Hyperventilation with respiratory alkalosisrespiratory alkalosis

Diagnostic criteriaDiagnostic criteria::

- arterial hypoxemia - arterial hypoxemia (PAO2/FIO2 <300)(PAO2/FIO2 <300)

- bilateral infiltrates on chest - bilateral infiltrates on chest radiograph in the absence radiograph in the absence of pneumonia and heart of pneumonia and heart failurefailure

Renal DysfunctionRenal Dysfunction

Proteinuria- renal failure Proteinuria- renal failure secondary to hypovolemia, secondary to hypovolemia, hypotension, renal hypotension, renal vasoconstriction and toxic vasoconstriction and toxic drugsdrugs

oliguriaoliguria

Gastrointestinal Tract injuryGastrointestinal Tract injury Hypoperfusion of visceral Hypoperfusion of visceral

organs leads to impairment of organs leads to impairment of the gut barrier function allowing the gut barrier function allowing the translocation of bacteria the translocation of bacteria into the lymph and blood into the lymph and blood streamstream

Aspiration of the microbial and Aspiration of the microbial and chemical contents of the upper chemical contents of the upper GI tractGI tract

GI bleedingGI bleeding IleusIleus

Hepatic DysfunctionHepatic Dysfunction

Cholestatic jaundice – elevation in conjugated Cholestatic jaundice – elevation in conjugated and unconjugated bilirubin(<10mg/dl)and unconjugated bilirubin(<10mg/dl)

Elevated alkaline phosphatase, bilirubin and Elevated alkaline phosphatase, bilirubin and aminotransferases are commonaminotransferases are common

Frank hepatic failure (“shock liver”) is uncommonFrank hepatic failure (“shock liver”) is uncommon

Cutaneous ManifestationsCutaneous Manifestations

Cellulitis and thrombophlebitisCellulitis and thrombophlebitis Ecthyma gangrenosum or bullous lesionsEcthyma gangrenosum or bullous lesions Symmetrical peripheral gangrene associated Symmetrical peripheral gangrene associated

with DIC, fibrin thrombi are seen in small with DIC, fibrin thrombi are seen in small vessels, but neither inflammatory cells nor vessels, but neither inflammatory cells nor bacteria are foundbacteria are found

DiagnosisDiagnosis

Timely diagnosis and early intervention are key factors in Timely diagnosis and early intervention are key factors in preventing morbidity and mortalitypreventing morbidity and mortality

1. History1. History

a. a. Clinical History (Underlying diseases)Clinical History (Underlying diseases) immunosuppression – cell mediated vs. humoralimmunosuppression – cell mediated vs. humoral diabetes mellitus – poor glycemic control diabetes mellitus – poor glycemic control ↑risk↑risk hormonal abnormalitieshormonal abnormalities chronic obstructive pulmonary disease- chronic obstructive pulmonary disease- ↑risk pneumonia and ↑risk pneumonia and

bronchitisbronchitis valvular and congenital heart disease - ↑risk of IEvalvular and congenital heart disease - ↑risk of IE hyposplenism or aspleniahyposplenism or asplenia MalignancyMalignancy cirrhosiscirrhosis malnutritionmalnutrition

DiagnosisDiagnosis

b. b. Medication History (provides clues to infection Medication History (provides clues to infection type and severity)type and severity)

Prior antimicrobial therapy –alters disease epidemiology Prior antimicrobial therapy –alters disease epidemiology and warrants broadening microbiologic differential and warrants broadening microbiologic differential diagnosis (resistant and unusual pathogens)diagnosis (resistant and unusual pathogens)

NSAIDS and corticosteroid therapyNSAIDS and corticosteroid therapy allergic reactionsallergic reactions drug-related adrenal insufficiencydrug-related adrenal insufficiency

DiagnosisDiagnosis

1. History1. History

c. Invasive procedure or surgery c. Invasive procedure or surgery

d. Obstetric and gynecologic historyd. Obstetric and gynecologic history

e. Social Historye. Social History

- travel history, residence, occupation, - travel history, residence, occupation, recreational activities, alcoholism, smoking, recreational activities, alcoholism, smoking, sexual historysexual history

DiagnosisDiagnosis

2. Physical examination2. Physical examination

a. a. Vital signs - temperature, Pulse, Blood pressure, Vital signs - temperature, Pulse, Blood pressure, respiratory respiratory raterateb. General findings- apprehensive, tachypneic, toxic or ill-b. General findings- apprehensive, tachypneic, toxic or ill-lookinglookingc. Skin- petechiae, ecthyma gangrenosum, c. Skin- petechiae, ecthyma gangrenosum, purpuric purpuric macules, rashes, cellulitis, furuncles, abscess, pustulesmacules, rashes, cellulitis, furuncles, abscess, pustulesd. heart murmursd. heart murmurse. lungse. lungsf. abdominal, rectal and pelvic examinationf. abdominal, rectal and pelvic examinationg. extremitiesg. extremitiesh. wound and soft tissuesh. wound and soft tissuesi. central nervous systemi. central nervous system

DiagnosisDiagnosis

3. Diagnostic microbiology3. Diagnostic microbiology a. Blood culturesa. Blood cultures- blood volumes (10-20 ml adults)- blood volumes (10-20 ml adults)- blood culture set number – 2 to 3 sets- blood culture set number – 2 to 3 sets- site selection- antecubital veins or upper extremities- site selection- antecubital veins or upper extremities

not from cathetersnot from cathetersb. Gram stains and other stainsb. Gram stains and other stainsc. Culturesc. Culturesd. Hematologyd. Hematologye. Coagulation studiese. Coagulation studiesf. Chemistries – electrolytes, hepatic and renal panels, CRP,f. Chemistries – electrolytes, hepatic and renal panels, CRP,

cytokine levelscytokine levelsg. Arterial blood gasesg. Arterial blood gasesh. Urinalysis h. Urinalysis

DiagnosisDiagnosis

3. Diagnostic microbiology3. Diagnostic microbiology i. Serologic testsi. Serologic tests

- acute and convalescent antibody titers- acute and convalescent antibody titersj. Radiologyj. Radiologyk. CT and MRIk. CT and MRIl. ultrasonographyl. ultrasonographym. Nuclear medicine imagingm. Nuclear medicine imaging

Severe Sepsis Therapy: Severe Sepsis Therapy: Standard CareStandard Care

Source controlSource control

AntibioticsAntibiotics

Hemodynamic supportHemodynamic support

Mechanical ventilationMechanical ventilation

Renal replacement Renal replacement therapytherapy

Sedation/analgesiaSedation/analgesia

Ensure adequate Ensure adequate

nutritionnutrition

Provide Provide hematological hematological supportsupport

Other supportive Other supportive measuresmeasures

Wheeler AP, Bernard GR. Wheeler AP, Bernard GR. N Engl J MedN Engl J Med. 1999;340:207-14.. 1999;340:207-14.

THANK YOU FOR YOUR THANK YOU FOR YOUR ATTENTION!ATTENTION!

Other Sources:Other Sources:1. Principles and Practice of Infectious Diseases1. Principles and Practice of Infectious Diseases

66thth edition, 2005 (Mandel et al) edition, 2005 (Mandel et al)

2. Approach to Infectious Diseases 2. Approach to Infectious Diseases

55thth edition, 2003 ( Reese and Betts) edition, 2003 ( Reese and Betts)

3. Washington Manual on Infectious Diseases3. Washington Manual on Infectious Diseases

2005 edition2005 edition

4. Harrison’s Principle of Internal Medicine4. Harrison’s Principle of Internal Medicine

1717thth edition 2008 edition 20085. Surviving Sepsis Campaign: International Guidelines 5. Surviving Sepsis Campaign: International Guidelines

for Management of Severe Sepsis and Septic Shock: for Management of Severe Sepsis and Septic Shock: 2008 2008 (Crit CareMed.  2008;36(1):296-327)(Crit CareMed.  2008;36(1):296-327)