department of emergency medicine auckland city hospital sepsis dr. peter jones emergency medicine...
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Department of Emergency MedicineAuckland City Hospital
SepsisSepsis
Dr. Peter JonesDr. Peter Jones
Emergency Medicine SpecialistEmergency Medicine Specialist
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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)
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Definitions Cont.Definitions Cont.
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
Department of Emergency MedicineAuckland City Hospital
Dear SIRS I don’t like you...Dear SIRS I don’t like you...
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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!
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Case 1Case 1554yr Samoan male4yr Samoan male
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
Department of Emergency MedicineAuckland City Hospital
Case 1Case 1554yr Samoan male4yr Samoan male
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
Department of Emergency MedicineAuckland City Hospital
Case 1Case 1554yr Samoan male4yr Samoan male
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Case 2Case 259 Male 59 Male
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
Department of Emergency MedicineAuckland City Hospital
Case 2Case 259 Male 59 Male
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Case 1Case 1554yr Samoan male4yr Samoan male
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
Department of Emergency MedicineAuckland City Hospital
PenicillinFlucloxacillinErythromycinGentamicinTrimethoprim Sulfamethoxazole
TetracyclinesAmoxycillin
Department of Emergency MedicineAuckland City Hospital
Case 2Case 259 Male 59 Male
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Case 1Case 1554yr Samoan male4yr Samoan male
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Novel TherapiesNovel Therapies
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
Department of Emergency MedicineAuckland City Hospital
Novel TherapiesNovel Therapies
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
Department of Emergency MedicineAuckland City Hospital
Novel TherapiesNovel Therapies
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Novel TherapiesNovel Therapies
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
Department of Emergency MedicineAuckland City Hospital
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
Department of Emergency MedicineAuckland City Hospital
Antimicrobial TherapyAntimicrobial Therapy
http://ahsl85_gl/FormularyGuide/http://ahsl85_gl/FormularyGuide/
Best GuessBest Guess
Department of Emergency MedicineAuckland City Hospital
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
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