department of emergency medicine auckland city hospital sepsis dr. peter jones emergency medicine...

Department of Emergency MedicineAuckland City Hospital

SepsisSepsis

Dr. Peter JonesDr. Peter Jones

Emergency Medicine SpecialistEmergency Medicine Specialist


ObjectivesObjectives

Understand the current nomenclatureUnderstand the current nomenclature

Know the local organismsKnow the local organisms

Understand the spectrum of presenting Understand the spectrum of presenting illnessillness

Get a handle on the basic treatmentGet a handle on the basic treatment

Introduce novel treatmentsIntroduce novel treatments


DefinitionsDefinitions

Sepsis = SIRS + InfectionSepsis = SIRS + InfectionSIRS = 2/4 ofSIRS = 2/4 of

Temp >38 or <36Temp >38 or <36HR >90HR >90

Respiratory Rate >20 or PRespiratory Rate >20 or PaaCOCO22 <32 (4.3kPa) <32 (4.3kPa)

WCC >12 or <4 or >10% bandsWCC >12 or <4 or >10% bands

Infection = eitherInfection = eitherBacteraemia (or viraemia/fungaemia/protozoan)Bacteraemia (or viraemia/fungaemia/protozoan)Septic focus (abscess / cavity / tissue mass)Septic focus (abscess / cavity / tissue mass)


Definitions Cont.Definitions Cont.

Severe sepsis = Sepsis + Organ Severe sepsis = Sepsis + Organ DysfunctionDysfunctionOrgan Dysfunction = Any of Organ Dysfunction = Any of

SBP <90 or 40 <usual or inotrope to get MAP 90SBP <90 or 40 <usual or inotrope to get MAP 90BE <-5mmol/LBE <-5mmol/LLactate >2mmol/LLactate >2mmol/LOliguria <30ml/hr for 1 hourOliguria <30ml/hr for 1 hourCreatinine >0.16mmol/LCreatinine >0.16mmol/LToxic confusional stateToxic confusional state

FIOFIO2 2 >0.4 and PEEP >5 for oxygenation>0.4 and PEEP >5 for oxygenation



Septic Shock = Severe sepsis + Septic Shock = Severe sepsis + HypotensionHypotension

Hypotension = eitherHypotension = eitherSBP <90 or 40<usualSBP <90 or 40<usual

Inotrope to get MAP >90Inotrope to get MAP >90


Dear SIRS I don’t like you...Dear SIRS I don’t like you...


High Risk PatientsHigh Risk PatientsFor SepsisFor Sepsis

Post op / post procedure / post traumaPost op / post procedure / post trauma Post splenectomy (encapsulated organisms)Post splenectomy (encapsulated organisms) Cancer Cancer Transplant / immune supressedTransplant / immune supressed Alcoholic / MalnourishedAlcoholic / Malnourished

For DyingFor Dying Genetic predisposition (e.g. meningococcus)Genetic predisposition (e.g. meningococcus) Delayed appropriate antibioticsDelayed appropriate antibiotics Yeasts and EnterococcusYeasts and Enterococcus SiteSite

For BothFor Both Cultural or religious impediment to treatmentCultural or religious impediment to treatment


Case 1Case 1554yr Samoan male4yr Samoan male

24 hr Fever and delirium, Arrive 1300hr24 hr Fever and delirium, Arrive 1300hrInitial ObsInitial Obs HR 162, RR 30, sats 95% on 15l, BP 116/82, HR 162, RR 30, sats 95% on 15l, BP 116/82,

GCS 13/15GCS 13/15

HistoryHistory Migratory abdominal pain and fever 1/7Migratory abdominal pain and fever 1/7

ExaminationExamination GCS 15, CNS, CVS, RS, GIT normalGCS 15, CNS, CVS, RS, GIT normal 160kg160kg


Differential DiagnosisDifferential Diagnosis(this list is not exhaustive)(this list is not exhaustive)

PancreatitisPancreatitisIscheamic GutIscheamic GutHypovolaemic shockHypovolaemic shock

GI bleed / AAA rupture / ectopic / dehydrationGI bleed / AAA rupture / ectopic / dehydrationCardiogenic shockCardiogenic shock

AMI / Myocarditis / TamponadeAMI / Myocarditis / TamponadePEPEToxic Shock SyndromesToxic Shock Syndromes

Staph AureusStaph Aureus Group A StrepGroup A Strep

Addisonian crisis (note relative adrenocorticoid insufficiency in Addisonian crisis (note relative adrenocorticoid insufficiency in many septic patients)many septic patients)Thyroid StormThyroid StormToxidromesToxidromes

Anticholinergic / serotoninergicAnticholinergic / serotoninergic


InvestigationsInvestigations

BasicBasicWBCWBC

PlateletsPlatelets

CoagsCoags

Renal functionRenal function

GlucoseGlucose

AlbuminAlbumin

LFTLFT

ABGABG

Specific ?SourceSpecific ?SourceUrineUrine

CxRCxR

Blood Cultures x 2Blood Cultures x 2

LPLP

AspirateAspirate

BiopsyBiopsy

May all be normal early on!


TreatmentTreatment

SpecificSpecific AntibioticsAntibiotics

Empiric based on sourceEmpiric based on source

Know local pathogensKnow local pathogens

Use the RMO guidelines / pharmacy handbook for best Use the RMO guidelines / pharmacy handbook for best guess treatmentguess treatment

Ideal to get cultures 1Ideal to get cultures 1stst but do not delay antibiotics but do not delay antibiotics SurgerySurgery

Get the pus out! All of it!Get the pus out! All of it!

Early definitive care will improve survivalEarly definitive care will improve survival


TreatmentTreatment

SupportiveSupportive Oxygenate / Ventilate (6ml/kg)Oxygenate / Ventilate (6ml/kg)

VolumeVolumeWill need more than ‘maintenance’ + replace losses with like Will need more than ‘maintenance’ + replace losses with like fluidfluidColloid v Chrystalloid (SAFE trial awaited – know the Colloid v Chrystalloid (SAFE trial awaited – know the results!)results!)

InotropesInotropesNoradrenalin is inotrope of choice, dopamine next Noradrenalin is inotrope of choice, dopamine next

Early ICU referral Early ICU referral


TreatmentTreatment

SupportiveSupportive

Electrolyte homeostasisElectrolyte homeostasisTHAM for pH <7.2 1-2mL / kg over 20minTHAM for pH <7.2 1-2mL / kg over 20min

Address co-morbidities Address co-morbidities ß-Blocker & reduced inotropyß-Blocker & reduced inotropyDM / COADDM / COADAlcoholism / malnutrition / steroidsAlcoholism / malnutrition / steroidsStop nephrotoxins (NSAIDs)Stop nephrotoxins (NSAIDs)

Early ICU referral Early ICU referral



InvestigationsInvestigations FBC, U and E, BC, MSUFBC, U and E, BC, MSU ABGABG

TreatmentTreatment IV Fluids IV Fluids

3l 0.9% Saline in 1.5 hours3l 0.9% Saline in 1.5 hours1l Gelofusin in 1.5hrs1l Gelofusin in 1.5hrs

IDUCIDUC AntibioticsAntibiotics

Gentamicin 320mg, Augmentin 1.2gmGentamicin 320mg, Augmentin 1.2gm

Past HistoryPast History April 2003 Left ureteric stone, 6mm April 2003 Left ureteric stone, 6mm Referred urology, discharge next day “GP FU” for USReferred urology, discharge next day “GP FU” for US



ResultsResults Urine Dip:Urine Dip: 500wbc, no nitirites, 200rbc 500wbc, no nitirites, 200rbc FBC: wcc 4.67, pmn 3.85 (0.47bands) plt 177FBC: wcc 4.67, pmn 3.85 (0.47bands) plt 177 Coag: Inr 1.1, Aptt 26, fibrinogen >7g/LCoag: Inr 1.1, Aptt 26, fibrinogen >7g/L U and E: Na 132, K 4.6, U 10.6, C 0.26U and E: Na 132, K 4.6, U 10.6, C 0.26 CRP 301.9CRP 301.9 ABG:ABG: pH 7.36, po2 23, pco2 5.3, hco3 22, be -2.7pH 7.36, po2 23, pco2 5.3, hco3 22, be -2.7 Lactate:Lactate: 3.0 3.0 CXRCXR



Progress 15:10 hoursProgress 15:10 hours Urology referral (accepted)Urology referral (accepted) DCCM referral (declined)DCCM referral (declined)

Renal imaging booked : CT Renal imaging booked : CT 11 22 Progressively hypotensiveProgressively hypotensive 55mL urine over 7 hours55mL urine over 7 hours

Declined all treatmentDeclined all treatment


Case 2Case 259 Male 59 Male

29/1029/10 Back pain, lifting fridgeBack pain, lifting fridgeTemp 37.3, HR 60 BP 130/60Temp 37.3, HR 60 BP 130/60

Tender lumbar area with slight reduction SLR / R leg powerTender lumbar area with slight reduction SLR / R leg power

PR normalPR normal

Rx Analgesia, mobilised, discharged homeRx Analgesia, mobilised, discharged home

1/111/11 Represents 1400Represents 1400Was getting better then worse again on mobilisingWas getting better then worse again on mobilising

Temp 35.8, HR 112 BP 150/80Temp 35.8, HR 112 BP 150/80

Asleep when reviewedAsleep when reviewed

Findings as above Findings as above →→Treated with analgesia, handed overTreated with analgesia, handed over

Kept overnight Kept overnight →→ Urine test done Urine test done



Urine:Urine: Trace blood +ve nitritesTrace blood +ve nitrites

LFT:LFT: “because patient thought he was “because patient thought he was jaundiced”jaundiced”

Bili Bili 23, GGT 167, ALP 157 (40-120) 23, GGT 167, ALP 157 (40-120) AST 60 (< 40), ALT 72 (< 45)AST 60 (< 40), ALT 72 (< 45)

U and E:U and E: Na 131. K 3.1, U8.4, C0.09Na 131. K 3.1, U8.4, C0.09

FBC:FBC: Normal (lympho 0.88)Normal (lympho 0.88)

Reviewed:Reviewed: MobilisingMobilising

Discharged with GP Follow up urineDischarged with GP Follow up urine



2/11/03 2/11/03 Self presented to White CrossSelf presented to White Cross Temp 38.8c, GP rang lab Temp 38.8c, GP rang lab →→ Staph Aureus Staph Aureus Referred medical ?pyelonephritis ?DiscitisReferred medical ?pyelonephritis ?Discitis BC doneBC done

ProgressProgress S/B med reg, Rx Flucloxacillin, stop NSAIDS/B med reg, Rx Flucloxacillin, stop NSAID

Delirium / L elbow bursitisDelirium / L elbow bursitis

MRI:MRI: 4/11/03 L2-3 discitis, L psoas abscess, 4/11/03 L2-3 discitis, L psoas abscess, epidural collection - decided not for drainageepidural collection - decided not for drainage

Discharge with ongoing PICC antibiotics 6 weeksDischarge with ongoing PICC antibiotics 6 weeks


Local SusceptibilitiesLocal Susceptibilities

There are current hospital There are current hospital recommendations based on local recommendations based on local susceptibilities and presumed site of susceptibilities and presumed site of infection on the intranet – USE THEM!infection on the intranet – USE THEM!

Look under Pharmacy, antimicrobial Look under Pharmacy, antimicrobial guidelines, best guess therapyguidelines, best guess therapy

Department of Emergency MedicineAuckland City HospitalAmoxycillin / Clavulanic AcidCefuroximeCeftriaxoneGentamicinNorfloxacinNitrofurantoinAztreonamTrimethoprim / Sulfamethoxazole



Microbiology resultsMicrobiology results Urine WCC Urine WCC >1000: RCC 310 million/L Bacteria : Present >1000: RCC 310 million/L Bacteria : Present

COLONY COUNT : 10 to 100 million/L CULTURE Mixed growth COLONY COUNT : 10 to 100 million/L CULTURE Mixed growth predominantly: predominantly:

(1) E. coli(1) E. coli (1) (1) Amoxycillin R Cephalothin S Cefuroxime S (1) (1) Amoxycillin R Cephalothin S Cefuroxime S Trimethoprim R Trimethoprim R Gentamicin SGentamicin S Cotrimoxazole R Norfloxacin S Cotrimoxazole R Norfloxacin S Amoxycillin/clav. SAmoxycillin/clav. S Nitrofurantoin S Nitrofurantoin S

PERIPHERAL BLOOD CULTURE PERIPHERAL BLOOD CULTURE ((1) E. coli1) E. coli (1) (1) Amoxycillin R Cephalothin S Cefuroxime S (1) (1) Amoxycillin R Cephalothin S Cefuroxime S

Ceftriaxone S Ceftazidime S Aztreonam S Trimethoprim R Ceftriaxone S Ceftazidime S Aztreonam S Trimethoprim R Gentamicin SGentamicin S Amikacin S Cotrimoxazole R Norfloxacin S Amikacin S Cotrimoxazole R Norfloxacin S Ciprofloxacin S Ciprofloxacin S Amoxycillin/clav. SAmoxycillin/clav. S Ticarcillin/clav. S Ticarcillin/clav. S Meropenem S Nitrofurantoin SMeropenem S Nitrofurantoin S


PenicillinFlucloxacillinErythromycinGentamicinTrimethoprim Sulfamethoxazole

TetracyclinesAmoxycillin



URINE MICROSCOPY WCC 170 RCC 30 Epithel. cells <10 URINE MICROSCOPY WCC 170 RCC 30 Epithel. cells <10 million/L Bacteria Present Granular casts 2 million/L million/L Bacteria Present Granular casts 2 million/L CHEMISTRY Protein : Moderate amount CHEMISTRY Protein : Moderate amount

COLONY COUNT : > 100 million/L CULTURE (1) COLONY COUNT : > 100 million/L CULTURE (1)

Staphylococcus aureusStaphylococcus aureus (1) (1) Penicillin R (1) (1) Penicillin R Flucloxacillin SFlucloxacillin S Cotrimoxazole S Doxycycline S Nitrofurantoin S Trimethoprim S Cotrimoxazole S Doxycycline S Nitrofurantoin S Trimethoprim S

PERIPHERAL BLOOD CULTURE (1) PERIPHERAL BLOOD CULTURE (1) Staphylococcus Staphylococcus aureusaureus (1) (1) Penicillin R Erythromycin S (1) (1) Penicillin R Erythromycin S Flucloxacillin SFlucloxacillin S Doxycycline S Doxycycline S


MetronidazoleAugmentinClindamycin

Department of Emergency MedicineAuckland City Hospital Amphotericin


Local Organisms 1999-2000Local Organisms 1999-2000ED / AAU / DCCM Positive BC 18/12, n=428

0

10

20

30

40

50

60

70

80

Organsim

Nu

mb

er

Pathogens

E.ColiS AureusS PneumoniaeViridans StrepKlebsiellaN MenS PyoE Cloacae


Local OrganismsLocal Organisms

Approx 45-55% positive ED BC are skin Approx 45-55% positive ED BC are skin organism contaminantsorganism contaminants

Similar across the hospitalSimilar across the hospital

This is approx 5% all BC doneThis is approx 5% all BC done

Always get at least 2 blood culturesAlways get at least 2 blood cultures Help sort out ?contaminantsHelp sort out ?contaminants



Subsequently declared incompetent by Subsequently declared incompetent by pyschiatry, then consented to treatmentpyschiatry, then consented to treatment Nephrostomy 21:30Nephrostomy 21:30 DCCM admission (3 days)DCCM admission (3 days)

NoradrenalinNoradrenalin

CPAP (OSA)CPAP (OSA)

Creatinine 0.10Creatinine 0.10

Discharged 2/12/03Discharged 2/12/03


Local OutcomesLocal Outcomes

Mortality from sepsis varies Mortality from sepsis varies

(Age, co-morbidity, illness severity)(Age, co-morbidity, illness severity)

DCCM data Auckland HospitalDCCM data Auckland Hospital 5-15% for meningitis / brain abscess / pid5-15% for meningitis / brain abscess / pid 20-35% for pneumonia / uti / abdominal20-35% for pneumonia / uti / abdominal 45-50% for mediastinum / joints45-50% for mediastinum / joints Data varies from other hospitals Data varies from other hospitals

? Due to Policies of DCCM for example? Due to Policies of DCCM for example Early tracheostomyEarly tracheostomy Admission criteriaAdmission criteria


Novel TherapiesNovel Therapies

Steroids Steroids JAMA. 2002 Aug 21;288(7):862-71JAMA. 2002 Aug 21;288(7):862-71

Many (>50%) septic patients have relative adrenocortical Many (>50%) septic patients have relative adrenocortical insufficiency.insufficiency.

Physiological hydrocortisone improves mortality in this group Physiological hydrocortisone improves mortality in this group (63% (63% →→ 53%, p=0.02 in this study, n=229) 53%, p=0.02 in this study, n=229)

AntiinflammatoryAntiinflammatory



Activated Protein C (Drotrecogin Activated Protein C (Drotrecogin αα) ) N Engl J Med. 2001 Mar 8;344(10):699-709N Engl J Med. 2001 Mar 8;344(10):699-709

Antithrombotic, antiinflammatory, profibrinolyticAntithrombotic, antiinflammatory, profibrinolytic

1690 patients, Mortality 30.8% 1690 patients, Mortality 30.8% →→24.7% p<0.0124.7% p<0.01

Increased bleeding 2% Increased bleeding 2% →→3.5% p=0.063.5% p=0.06 Caution in meningococcal sepsis / trauma / ICH / pregnant!Caution in meningococcal sepsis / trauma / ICH / pregnant! $17181 / patient$17181 / patient Consensus in NZ is restricted last resort use in selected ICU Consensus in NZ is restricted last resort use in selected ICU

patientspatients



Tight glucose control with insulin Tight glucose control with insulin

N Engl J Med. 2001 Nov 8;345(19):1359-67. N Engl J Med. 2001 Nov 8;345(19):1359-67.

Mortality reduction 8Mortality reduction 8→4.6% (p<0.04) all icu →4.6% (p<0.04) all icu patientspatientsBiggest reductions in severe sepsis / long Biggest reductions in severe sepsis / long stayersstayersAlso reduced bacteraemic episodes / icu Also reduced bacteraemic episodes / icu neuropathy neuropathy Aim 4.4-6.1mmol/LAim 4.4-6.1mmol/L



rBacteriocidal/Permeability-increasing rBacteriocidal/Permeability-increasing proteinprotein In neutrophil granulesIn neutrophil granules Binds to and inactivates endotoxin Binds to and inactivates endotoxin

Lancet. 2000 Sep 16;356(9234):961-7.Lancet. 2000 Sep 16;356(9234):961-7.

393 Children with clinical meningococcaemia393 Children with clinical meningococcaemia

Mortality 9.9% Mortality 9.9% →→ 7.4% p=0.48 7.4% p=0.48

Amputations 7.4% Amputations 7.4% →→ 3.6%, p=0.067 3.6%, p=0.067

Better functional outcome 66.3% Better functional outcome 66.3% →→ 77.3% p=0.019 77.3% p=0.019


Novel TherapiesNovel TherapiesSummarySummary

Reducing mortality in sepsis: new Reducing mortality in sepsis: new directionsdirections Critical CareCritical Care 2002, 2002, 66(Suppl (Suppl 3)3)::S1-S18 S1-S18 (http://ccforum.com/content/6/S3/S1 )(http://ccforum.com/content/6/S3/S1 )

This is highly recommended reading, concise reviews of This is highly recommended reading, concise reviews of Low tidal volume ventilationLow tidal volume ventilation Early goal directed therapyEarly goal directed therapy Drotrecogin alfa (activated)Drotrecogin alfa (activated) Moderate dose corticosteroidsModerate dose corticosteroids Tight control of blood sugarTight control of blood sugar



NAC NAC Crit. Care. Med. 2003 31 (11) 2574-78Crit. Care. Med. 2003 31 (11) 2574-78

Nuclear factor-Nuclear factor-κκB controls expression B controls expression inflammatory mediatorsinflammatory mediators

NAC inhibits NFKB in vitroNAC inhibits NFKB in vitro Pilot trialPilot trial

20 patients, randomised20 patients, randomised

72 hrs NAC or placebo72 hrs NAC or placebo

IL-8 suppressed (may be implicated in lung injury)IL-8 suppressed (may be implicated in lung injury)

Recommend larger human trialsRecommend larger human trials


SummarySummary

Sepsis may be obvious or subtle earlySepsis may be obvious or subtle earlyThere is a high mortality and morbidityThere is a high mortality and morbidityHave a high index of suspicionHave a high index of suspicionKnow local organisms / susceptibilitiesKnow local organisms / susceptibilitiesTake appropriate culturesTake appropriate culturesTreat early and aggressivelyTreat early and aggressivelyInvestigate early and aggressivelyInvestigate early and aggressivelyRefer early and aggressivelyRefer early and aggressivelyBe aware of new developmentsBe aware of new developments


Antimicrobial TherapyAntimicrobial Therapy

http://ahsl85_gl/FormularyGuide/http://ahsl85_gl/FormularyGuide/

Best GuessBest Guess


More ReferencesMore References

Streat S Orientation Lectures for Medical Staff DCCM Streat S Orientation Lectures for Medical Staff DCCM 12/1/2004 – This hospital’s approach12/1/2004 – This hospital’s approach

Bone RC Chest 101: 1644, 1992 (Definitions) Bone RC Chest 101: 1644, 1992 (Definitions)

Vincent JL Crit Care med 1997 25(2) 372-74 Dear SIRS Vincent JL Crit Care med 1997 25(2) 372-74 Dear SIRS -editorial-editorial

Angus DC Crit Care med 2001 29 (suppl) 7 s109-s116 –Angus DC Crit Care med 2001 29 (suppl) 7 s109-s116 –epidemiologyepidemiology

Klinzing S Crit Care med 2003 31 (11) 2626-50 – Klinzing S Crit Care med 2003 31 (11) 2626-50 – inotropesinotropes

department of emergency medicine auckland city hospital sepsis dr. peter jones emergency medicine...

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