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FromFever toSeptic Shock

https://my.vanderb i l t.edu /sep sismon ito r/p rogres s-repo rts /

Fever

http ://co l l id er.com/movie/article.asp / aid /4 8 6 7 /tcid /1

Fever• Normal human physiologic temperature rangesabove and

belowmean of ~98F(controversial)• Temperature above 99.5Fconsidered fever(also controversial)• Majorityof research todatedoes notsupport harm from

febrile state.– Threemain exceptions:• Feverd/theatstroke• Fevercausing extrememetabolic demands in ptswithunderlying cardiac and pulmonary disorders• Feverinelderlyprone tomentaldysfunction

• Research todateand variousguidelines:•Recommend onlysuppressing fevertoprovidepatientcomfort•Findan increase inviralshedding andprolonged diseasestateswithAspirinand Tylenoluse

EtiologyofFever

• Mostcommonreasonsforfeverinclude:– Infection(toagreaterextentbacterial)– Malignancies– Connectivetissue/autoimmunediseases

• Othernotascommonreasons:– Postoperative– Drugs/Medications– Undiagnosedillnesses

• Otherfactorsthatcancausefever:– Tachycardia,diurnalpatterns,ovulation,exercise,digestion,trauma,psychologicaldistress/disorders,infarction,burns,renalfailureandshock,burns,tissueinfarction,childbirth

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FeverPathophysiology

http ://d rraj ivd esaimd .com/tag/ch i l l srigo rs /

Pyrogens

• Exogenouspyrogens:– Microorganismsandtoxinsorotherproductsofmicrobialorigin,which inducemainlymacrophages toproduceendogenouspyrogens

• Endogenouspyrogens:– Cytokines (mainly IL-1,IL-6,TNF-alpha, interferonandprostaglandins)

– Antigen-antibody complexesassociatedwithcomplement

– Lymphocytederived molecules– Bileacids– Androgenic steroidmetabolites (naturalandsynthetic)

Fever inSOAP

FeverinSOAP• Exam:– PMH– Medicationreview– Recenttravel,exposuretopetsandotheranimals,otherexposure

– Familyhx:rarehereditarycausesoffever– Verifyfever:noresearchsupportforbestlocationtoverify(inadults)

– Pattern:continuous,relapsing,etc…• Labteststoconsider: CBCwithdifferential,CMP,UAC&S,CXR,ECG,ESR/CRP,ANA,Monospot,TBskintest,HIV,Heppanels

• Otherimagingperexamfindingsorindexofsuspicion

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Systemic Inflammatory ResponseSyndrome(SIRS)

• Thesystemic responsetoawide range ofstresses• Twoormoreofthe following:– Temp: >38C– HR:>90– RR:>20– PaCO2:<32– WBC:>12Kor<4K or>10%bands

SIRSDifferentialDiagnosis• Infection• Malignanthyperthermiaandheatstroke• Burns• Trauma• Pulmonaryembolism• MI• Cardiactamponade• Dissectingorrupturedaorticaneurysm• Occulthemorrhage• Adrenalinsufficiency• Thyroidstorm• Pancreatitis• Drugoverdose• Drughypersensitivityreactions

OtherSepsisDiagnostic Criteria

IDSA,2 0 1 3

• Hypothermia <36C• AMS• Significantedema or+fluidbalance• Hyperglycemia >140withDMhx• Elevated CRPand/orESR• Elevated procalcitonin• Arterial hypotension:<90SBP,MAP<70• Arterial hypoxemia:PaO2/FiO2<300• Acute oliguria:<0.5ml/kg/hr forat least2hoursdespiteadequate fluid

resuscitation• Creatinine >0.5mg/dL• Coagulationabnormalities: INR>1.5oraPTT >60• Ileus• Thrombocytopenia: plt <100K• Hyperbilirubinemia: TB>4• Decreased capillaryrefilland/ormottling• Lactic acid>2mmol/L

Elevated Lactic AcidLevels• Hyperlactatemia:>2• Lacticacidosis:>4• Twotypes– TypeA(tissuehypoxemia)

• Hypovolemia– Shock

– TypeB(withoutwidespreadtissuehypoxemia)• DKA• Sz d/o• Catecholamine release: exogenous orendogenous• Malignancy• ETOHism• Drugs:

– HAART– Propofol– Linezolid

• Mitochondrialdisorders

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Sepsis• Sepsisisthepresenceinfectiontogetherwithsystemicmanifestationsofinfection• Apartfromleukopeniaandhypothermia,sepsiscanbeanormalmanifestationofthebodiesimmuneresponseanddoesnotnecessarilysignifyaresultingpoorprognosis• Thetermsepticisaninformaltermforseveresepsisorsepticshock• Bacteremia:–Culturablebacteriainthebloodstream–Maybetransientandinconsequential–Inconsistentcorrelationwithseveresepsis

Sepsis• Leading cause ofinfectious death inU.S.• Costs ~25billion in hospital management• ~20-60% mortality rate in ~750K cases inUSannually

• >60% ofthese patients >65yearsold• ½Gram +s,½Gram (-)s, Candida• Foci ofinfection:– #1Lungs– #2“Urine”

• 100-300X greater forHD patients

SevereSepsis

IDSA,2 0 1 3

SevereSepsis•Mostcommonsitesforprimaryinfectioninpatientswithseveresepsisarethelungsandtheabdomen• Themostinfluentialfactorsforprogressingtoseveresepsis/shockare:• Surfaceareaofinfection• Severity• Susceptibilitytotreatment

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Septic Shock• Sepsiswithhypotensiondespiteadequatefluidresuscitationwithnootherunderlyingetiology

• Hypotension:<90systolic,<70MAP,or>40changefrombaseline

• Tachyphylaxistocatecholamines,corticosteroidsandaldosterone

• IncreasinglactateandH+,hyperphosphatemia• FurtherdepletionofATPstores,resultinginionpumpdysfunction:intracellulardecreaseinKandincreaseinNaandCa,leadingtocellularswelling,immenseROSactivity,cessationofproteinsynthesis,thenapoptosis

PRRs,PAMPs&DAMPs

http ://fo rmu lacro ssfi t.com/in flammato ry-r em ar ks-on -the-in flamm ato ry-p ro c es s/

PAMPs• LPS• Otherlipoproteins• Peptidoglycans• Zymosan(yeast)• Viralcoatproteins• Bacterialflagellin• Nucleicacids

*SmallsubsetofvarietyofPAMPsrepresented.WhenbindingwithPRRscreateinflammatorycascadeviareleaseofchemicalmediators(cytokines)

CellSignalingMolecules

http ://www.genecopoeia.com/p rodu ct/se ar ch /pathw ay /h_in flamP athw ay.php

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CellSignalingMolecules• Cytokines:– Eitherinflammatoryofinflammatory– Interleukins(ILs)– Interferons– Chemokines

• Histamine:– Vasodilationofmicrocirculation(capillarybeds,arterioles,venules)andvasoconstrictionoflargevessels

• Leukotrienes:– Actsimilartohistamine

• Prostaglandins:– Lipidsderivedfromcyclooxygenases(COX1,2)– Moderatecontractionofsmoothmuscles– Regulateinflammation

AcutePhaseResponse

http ://www.pharmatu to r.o rg/articles/in t erleu kin s-in -th er apeu tic s

AcutePhaseResponse• Thethreecharacteristicchangesinthemicrocirculation(arterioles,venules andcapillaries)include:–Bloodvesseldilation,increasedvascularpermeabilityandwhitebloodcellmigrationtolocalizedsiteofinnateimmunedetection(leukocytosis)

• Pain: afferentsignalsalongnociceptiveneuralpathways• Fever: IL-1,IL-6,TNF-alpha,interferonandprostaglandinsactingaspyrogens:

• Altertemperaturesetpoint,andstimulatelivertosynthesizebulkofinitialinflammatoryresponseproteins

• C-reactiveprotein:• Increasesactivityofphagocytesandfacilitatesthedeliveryofhumoral (antibodies)andcellularcomponents(TandBcells)tositesofinflammation.

AcutePhaseResponse• Anti-inflammatory:–Samemechanismscausingwhitebloodcellproliferationtoinfectedorinjuredtissuealsocanlimitabilitytoadhereandenterun-inflamedvascularendothelium.–Otherresponsesthatminimizeinflammationinclude:• Releaseofneuroendocrinehormones:cortisol,epinephrineandantioxidants

•Metabolicchanges:–IncreasedTSH,vasopressin,insulin,glucagon,catabolismofmuscleprotein

•Also:–Norepinephrine–Hepaticlipogenesis–Lipolysisinadiposetissue

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AcutePhaseResponse• Constitutional: fever, wt. loss,nightsweats, chills, rigors,myalgias, arthralgias, sleep, appetite, pain, lethargy

• HEENT: headache, photophobia,earcongestion/drainage, diplopia, conjunctivitis, rhinitis,hoarseness,pharyngitis, lymphadenopathy

• Cardio: chestpain (pleuritic),palpitations,edema

• Pulm: dyspnea,cough(+/- productive)

• GI: N/V, diarrhea, hematochezia, suppurative discharge

AcutePhaseResponse

• GU: dysuria, frequency, urgency,voidvolume,incontinence,posterior/flank pain

• MS: ROM,coordination,ataxia,muscleweakness

• Neuro: impaired mentation/consciousness, seizure,vertigo, sensation,CNimpairment

• Skin: rash/lesions,urticaria, erythrema

• Psych: depression,anxiety, mood lability

PathophysiologyofSevereSepsis• Abnormalfunctioninmicrocirculatoryunits(arterioles,venulesandcapillarybeds)

• DiminishedaccesstoO2foraerobicrespiration,thisdiminishestheATPneededforlife

• Multi-organfailureisasystem-wideorgan“hibernation”• Mismatchedratioofpro-inflammatorytoanti-inflammatorycytokines

• Desensitizationofphagocytestocomplement• Alterationofcoagulationcascades:– IncreasedtissuefactorsandVonWillibrandfactorfromincreasingcellulardebrisanddamagedendothelialtissue

– Increasedactivationofplatelets– Formationofmicrothrombi,leadingtodisseminatedintravascularcoagluation

MicrobialTriggersforSevereSepsis/Shock•Majorityofseveresepsisisassociatedwithcommensalbacterialandfungi–Entericgramnegativebacilli,coagulasenegativestaphylococci,enterococci,andCandidasp.

•Culturepositiveandculturenegativecaseshavesimilarmorbidityandmortality*•Bacterialendotoxins:–Scantevidencetheseplaylargeroleinseveresepsisbuttheystillcausesignificantcellulardamagetoareasoflocalizedextravasculartissue

• Superantigens(toxicshocksyndrometoxins):–BindtobroadrangeofTLRsviaMHCII,resultinginexcessivecytokinesandotheracutephasechemicalmediators– S.aureus,S.pyogenes,C.perfringens,V.vulnificus,filoviridae

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SevereSepsis/Septic Shock Manifestations:Nervous andEndocrine Systems

• Alterationsinhighercerebralfunctionareoftenearlymanifestationsofseveresepsis,particularlyinolderadults

• Focalneurologicalsigns:seizuresandcranialnervepalsiesarerare

• Hypothalamic-pituitaryadrenalaxis:– Bluntedreleaseofgrowthhormone,ACTH,prolactin

• Adrenalinsufficiency:– Cytokineinduceddysfunction,glucocorticoid

tachyphylaxis, prolongedinflammatorystates,hypoglycemia

• Autonomicdysfunction:– Abnormalitiesinheartrated/talterationsinsympatheticoutputortachyphylaxis

SevereSepsis/Septic Shock Manifestations:Bloodstream

• Neutrophilicleukocytosisisthenormalresponsetobacterialorfungalinfection

• Lymphocytosisinviralinfections• Thrombocytopenia• Plasmalipids:increaseintriglycerides,freefattyacidandvLDL• Glucose:initialhyperglycemiabutcanprogresstohypoglycemia• Lacticacid• Clotting:– DICin~50%ofindividualswithseveresepsis– CBCwithdiffandperipheralsmear,aPTT/PT,D-dimer,fibrinogen

SevereSepsis/Septic Shock Manifestations:Lungs

• Hyperventilationwithrespiratoryalkalosisisoneoftheearliestmanifestationsofsepsis

• ALI(acutelunginjury):PaO2/FIo2=<300• ARDS(acuterespiratorydistresssyndrome):bilat.pulm.infiltratesw/oHForPNAwithPaO2/FIo2=<200

• Diffusealveolarepithelialinjury leadingtofluidspillingintointerstitialandairspacecompartments

• Neutrophilsandmonocytesaggregatinginpulmonaryvessels• Pulmonaryshunting• Deadspacevolumeincreasesandcompliancedecreases• Intubationandmechanicalventilation

SevereSepsis/Septic ShockManifestations:GITract

• Increasedtranslocationofbacteriaintothelymphsystemandbloodstream

• Aspirationofmicrobialcontentsintothetracheobronchialtree• SmallerosionsofthegastricandduodenalmucosawhichresultsinupperGIbleeding andileus

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SevereSepsis/Septic ShockManifestations:Kidneys

• Fromminimalproteinuriatoprofoundrenalfailure• Oliguria• Azotemia• Uremia

SevereSepsis/Septic Shock Manifestations:Liver

• Cholestaticjaundice• Completehepaticfailureisrare

SevereSepsis/Septic Shock Manifestations:Skin

• Localized:pustules,cellulitis,eschar• Seedinginfections:pustules,cellulitis,petechiae• Diffuseeruptions:– Bacterialtoxins-hemorrhagiclesions– DICassociatedperipheralgangrene-necroticlesions

SevereSepsis/Septic Shock Manifestations:Immunity

• Immunedysfunction:– Highsusceptibilitytonosocomialinfectionsandcommensalinfections

– ReactivationoflatentherpessimplexandCMVoccursin~40%ofseveresepsispatients

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Surviving Sepsis

IDSA,2 0 1 3

SurvivingSepsis

• Obtainbloodculturesx2(aerobicandanaerobic)beforeadministrationofantimicrobialtherapyifdoesnotdelaytreatmentfor>45minutes• Drawculturespercutaneouslyandfromeachvascularaccessifnotplaced48hourspriortocontact• Culturesfromurine,CSF,wounds,respiratorysecretions,etc• Theadministrationofbroad-spectrumantimicrobialswithin1hourinpatientswithseveresepsisandsepticshock• Sourcecontrol:necrotizingsofttissueinfections,peritonitis,cholangitis,intestinalinfarction,intravascularaccessdevices,etcwithappropriaterapidconsultation

ContinuingSepsisTreatment• De-escalate antibiotics: targetingbothpurported species and

sensitivity• Procalcitonin• Use ofcrystalloids for fluid resuscitation, albuminwhere

substantial crystalloidsareneeded• Vasopressors:

– Norepinephrine as firstchoice (dopamine asalternativeonlyinhighlyselected patients)

– Epinephrine assecond add onorsecond choice– Vasopressin next– No lowdose dopamine forrenal protection

• Inotropic therapy:– Trialdose of dobutamine withsigns ofmyocardial dysfunction:elevatedcardiac fillingpressures, lowcardiac output

• Insome patients,hydrocortisone

Continuing Sepsis Treatment

• Tightglucosecontrol• PRBCinfusiononlywhenHgbisbelow 7g/dL• Platelets onlywhen<10Kwithoutbleeding and<20Kwithactive bleeding

• Continuousorintermittent hemodialysis• Intubationandmechanical ventilation management• Entericnutrition• Stressulcerprophylaxis• DVTprophylaxis• Decubitusulcerprophylaxis

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Sepsis Workup

• CBCwithdifferential, CMP,Mg,Phos.,IonizedCa• Lacticacid(q2until<2)• Procalcitonin• ABG• Coag.Panel, fibrinogen• CXR,UA,BCs(PCR),Resp.Cx andgram stain(PCR)• Legionella Ag, S.pneumoniae Ag• C.diff.PCR• InfluenzaA&BPCR

Procalcitonin (PCT)

• Usualcourse=cleavage intocalcitonininthyroid• Extrathyroidal non-neuroendocrinecleavage= mainlywithincreased concentrationsduringbacterial infectionbut*

• DAMPs+PAMPs= increase inlevels• Sepsisvs.SIRSofnoninfectiousorigin: LungsandGI• Levelspeak at6hours,plateau at~8-24hours,canremainelevated fordays-weeks after infection

• Differentbaselineand infectiondrivenPCT levels forCKDpatients

Procalcitonin (PCT)

Brecho t et al . , 2 0 1 5

Procalcitonin (PCT)

Grace and Tu rner,2 0 1 4

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Multiplex PCR• 1-2dayswithBCsvs hourswithPCR• AmplifiesDNAoflargespectrumofinfectiousbacteria• Decreased treatment ofcontaminants• Earlier administration ofdirectedABXsorde-escalation ofABXs

• Minimized resistance• ~25%reductionof#ofbroadspectrumdays

AntibioticResistance

http ://www.tu fts.edu /med /apua/abou t_issue /an tib io tic_r es _4 _2 8 2 6 0 3 7 9 0 3 .JPG

Anti-infective Therapy

http ://upend rats.b lo gspo t.com/2 0 1 2 /0 6 /an tib io tic-

h ttp ://www.thebody.com/con ten t/art8 7 5 .h tml

Anti-infective Therapy• Identificationoftheinfectingorganism:– Cultures,immunologicassaysandmoleculartesting(PCR)beforestartingdrugtherapy

• Inmostcases,offendingagentwillneverbefound:– Aimformostprobableoffendingagents:• Cellulitisinnon-immunocompromised individual(S.aureus,S.pyogenes)• Acuteotitismediainyoungchild(viralvs.H.influenzae,S.pneumoniae.M.catarrhalis)

• Hostfactors:– Hx ofpreviousadversereactionstoantimicrobialagents– GastricpH:absorptionincreasesordecreasesdependingon

pHanddrug– Renalfunction:• Decreasedinveryyoungchildrenandolderadults• Mostimportantrouteofeliminationforantimicrobialproducts:adjustmentneededrenalfunctionforandadequatedosing

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Anti-infective Therapy– Hepatic function:watchoutforazithromycin, Zosyn,

clindamycin,metronidazole, fluconazole,nitrofurantoin,isoniazid

– G6PD(glucose-6-phosphatedehydrogenase deficiency:hemolytic reactions tonitrofurantoin andBactrim

– DMII:hypoglycemic reactions toBactrim– Pregnancy: increased clearance, notetracyclines

(includesbreast-feeding)• Siteofinfection:drug tositeofinfection(penetrance):– Bile-concentrated, blood-brainbarrier, bone,etc– Routeofadministration:oralvs.parenteral

• Removal offoreignmaterial: prostheticsandimplants

Bacteria

http ://www.d reamstime.com/pho to s-im ag es /bac teri a.h tml

Gram+AerobicCocciGram+aerobiccocci:• Coagulasepostive (Staphyloccous aureus)• Coagulasenegative:S.epidermidis andothercommensalsStreptococcus:Lancefieldantigenandhemolyticreaction

S.pyogenes (strepthroatandnecrotizingfasciitis)S.pneumoniaeS.AgalactiaeViridans streptococci(usuallycontaminants,commensals)

Treatment:Penicillins (alltypes),Cephalosporins,Clindamycin,Vancomycin,Daptomycin,Linezolid,Orbactiv (oritavancin),Sivextro (tedizolid),Dalvance (dalbavancin)

Gram+AerobicCocci

http s://ro jo sonmed icalcl in ic.wo rdp ress.com

h ttp ://l in k.sp rin ger.com/referen cewo r ken t ry

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Gram+Aerobic Bacilli (Rods)

http ://textbooko fb acterio lo gy.n et/An th rax.h tml

• Listeriamonocytogenes

• Bacillusanthracis

Gram+AnaerobicBacilli (sporeforming)

• Clostridiumtetani• C.botulinum• C.perfringens• C.difficile

h ttp ://www.cd i ff-suppo rt.co .u k/abou t.h tm

OtherGram+

http ://o ccupational -th erap y.ad van ceweb .co m/f eatu r es/ arti cles /vr e-sti l l -re sistin g

• Enterococcusfaecalis• E.faecium

Gram(-) Aerobic Cocci

http ://www2 .wlu .edu /x5 1 8 3 4 .xml

• Neisseriameningitidis• N.gonorrhoeae• Moraxellacatarrhalis

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Gram(-) Aerobic Bacilli

http ://www.natu re.com/natu re/jou rnal/v4 0 6 /n6 7 9 5 /fig_tab/

• Vibrio cholerae• V.vulnificus• H.pylori• Pseudomonasaeruginosa

Gram(-)AerobicBacilli:Enterobacteriaceae

http ://www.mrsaidb lo g.com/tag/c arb ap enem-r esist an t-en t erobact eri ac ea e/

• E.coli• Klebsiella• Citrobacter• Enterobacter• Morganella• Proteus• Salmonella• Yersiniapestis

OtherGram(-)

http ://textbooko fb acterio lo gy.n et/h aemoph i lu s_2 .h tml

• H.Influenzae• Legionellapneumophila• Captocytophaga

canimorsus

Spirochetes

http ://news.n ationalgeograph ic.com/news/2 0 1 4 /0 2 /1 4 0 2 2 8 -

• Syphilis(Treponemapallidum)• Lymedisease(B.burgdorferi)

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Mycoses

http ://servin gnatu re.b lo gspo t.com

Viruses

http ://www.fromquarkstoquasars.com/rh inopharyngi ti s

• Lungs:– Non-Pseudomonas

• Rocephin +Azithromycin• Levaquin

– Pseudomonas• Cefepime orAztreonam +Levaquin orCarbapenem

– Pseudomonas +MRSARisk• Cefepime orAztreonam +Levaquin orCarbapenem +Vancomycin

• Meningitis– Rocephin or IDconsult +Vancomycin

• Intra-abdominal– Zosyn orLevaquin orFlagyl

Antibacterials

• Skin– Vancomycin +Clindamycin+Zosyn orAztreonam

• Line sepsis– Vancomycin +Cefepime orLevaquin

• Urine– Cefepime orAztreonam +Levaquin

• Neutropenic fevers– Vancomycin +Cefepime orAztreonam orLevaquin

Antibacterials

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• Zosyn:– Coag.abnormalities– Thrombocytopenia– Jarisch-Herxheimer reaction– Seizures(renalfailure)

• Levaquin:– QTprolongation– Cautionwithelectrolyteabnormalities– Hypoglycemia– Tendonrupture– CautioninSz d/o

Antibacterials

• Cefepime:– IncreasesINR– Encephalopathy,mycoclonus,seizures

• Rocephin– INRabnormalities

• Azithromycin– QTprolongation,cautionwithelectrolyteabnormalities– Cautionwithbradycardia,uncompensatedHF,

antiarrthymics

Antibacterials

– Azoles(voraconazole,etc)– Echinocandins (caspofungin,micafungin)– AmphotericinB– Bactrim

Antifungals• Acyclovir

• Reactivation– HSV– CMV– EBV– HepatitisB

Antivirals

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• +Fluid balanceà steadystatefluid balanceà (-)fluidbalance

• CHFandCKD

• Crystalloids– 30ml/kgbolus– maintenance fluids– NSvs LR

• Colloids– Albumin(nodefinitiveanswerfromresearch)– Starches=AKI

Fluid Resuscitation

• Greaterdendriticcellresponse=greatermagnitudeandtimeofsepsispresentation

• Glucocorticoids mutedendriticcellresponse• Duringsepsisincreasedchemicalmediator

concentrations=bluntedadrenalcorticosteroidproduction

• Additionofexogenouscorticosteroidsdecreasesmagnitudeandtruncateslengthofpresentationbutincreasesriskofrecurrentinfection

• Hydrocortisone

Corticosteroids

• Nocurrentresearchsupportedrecommendationsbutinpractice

• IndicatedforESRDorrenaltubularacidosispatientswithconcurrentsepsis

• pH<7.2• Issues– Naoverload thus fluid overloadalso– Increases lactateandpCO2 levels– Decreases ionized Ca levelswhich resultsindecreased CO

Sodium Bicarbonate• Hyperglycemic variability s/tproinflammatory

mediators (cortisol, catecholamines, cytokines)• Prothrombotic effects• Decreased endothelial vascular reactivity• Decreased function ofneutrophils

• Insulin gtt-short acting– GoalBG140-180

Dysglycemia and Sepsis

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• Netcatabolicstate– Decreased carbs, protein and lipids

• Anorexia• Encephalopathy• Mechanicalventillation

• ~6daydelayinnutritionalsupplementation– Enteral first!

Metabolism andSepsis

Englert and Rogers, 2 0 1 6

• AssociatedwithCAP– Extendeddurationoffebrilestate– Increasedlengthofhospitalstay– Increasedlikelihoodofempyemas andARDS

• Minimizesimmunefunction– Neutrophil andMacrophageactivity

• Increasedproinflammatory cytokines

• Increasedintestinalpermeability=bacterialtranslocation

• Decreasedciliaandsurfactantfunction

• Increasesriskofaspiration

• Poordentalhygiene

• Minimizescoughreflex

• Malnutrition

ETOHuse and sepsisAbouDagher,Gilbertetal. (2015).Sepsis inhemodialysis patients.BMCEmergencyMedicine, 15(30)

Brechot,Nicolas,Hekimian, Guillaume, Chastre,JeanandLuyt,Charles,Edouard.(2015).Procalcitonin toguideantibiotic therapy intheICU.InternationalJournalof Antimicrobial agents,46,S19-S24

Englert, JoshuaandRogers,Angela.(2016).Metabolism,metabolomics andnutritional supportofpatientswithsepsis. Clinics inChest Medicine

Grace, Eddie andTurner,Mackenzie. (2014).Useof procalcitonin inpatientswith various degress of chronickidney disease including renal replacement therapy.Clinical Practice,59(12) ,1761-1767

Larkin, Caroline,Santos-Martinez,Maria-Jose,Ryan,Thomas, andRadomski,Marek. (2016).Sepsis-associatedthrombocytopenia.Thrombosis Research,141,11-16

Mandell, Gerald, Bennett,JohnandDolin,Raphael,Principles andPracticeof Infectious Diseases,7thE

Plummer,MarkandDeane, Adam.(2016).Dysglycemiaandglucosecontrolduring sepsis.Clinics inChestMedicine

References

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Sasko, Benjaminetal. (2015).Earliest bedsideassessment of hemodynamic parameters andcardiac biomarkers:their roleof predictors of adverseoutcomeinpatientswith septic shock.InternationalJournalof MedicalSciences, 12(9) ,680-688

Semler, MatthewandRice,Todd.(2016).Sepsis resuscitation:f luidchoiceanddose.Clinics inChest Medicine

Robinson,Richard.(2015).Glucocorticoidsreducesepsisbydminishingdendriticcellresponses.PLOSBiology,DOI:10.1371/journal.pbio.1002270

Velisarris etal. (2015).Theuseif sodiumbicarbonateinthetreatment ofacidosis insepsis:aliteratureupdateonalongterm debate.Critical Care Research andPractice, ArticleID605830

http://survivingsepsis.org/Guidelines/Pages/default.aspx

CDC

IDSA

WHO

References