Sepsis
Dr. Peter Jones
Emergency Medicine Specialist
Department of Emergency Medicine
Auckland City Hospital
Objectives
Understand the current nomenclature
Know the local organisms
Understand the spectrum of presenting
illness
Get a handle on the basic treatment
Introduce novel treatments
Department of Emergency Medicine
Auckland City Hospital
Definitions
Sepsis = SIRS + Infection
SIRS = 2/4 of
Temp >38 or <36
HR >90
Respiratory Rate >20 or PaCO2 <32 (4.3kPa)
WCC >12 or <4 or >10% bands
Infection = either
Bacteraemia (or viraemia/fungaemia/protozoan)
Septic focus (abscess / cavity / tissue mass)
Department of Emergency Medicine
Auckland City Hospital
Definitions Cont.
Severe sepsis = Sepsis + Organ
Dysfunction
Organ Dysfunction = Any of
SBP <90 or 40 <usual or inotrope to get MAP 90
BE <-5mmol/L
Lactate >2mmol/L
Oliguria <30ml/hr for 1 hour
Creatinine >0.16mmol/L
Toxic confusional state
FIO2 >0.4 and PEEP >5 for oxygenation
Department of Emergency Medicine
Auckland City Hospital
Definitions Cont.
Septic Shock = Severe sepsis +
Hypotension
Hypotension = either
SBP <90 or 40<usual
Inotrope to get MAP >90
Department of Emergency Medicine
Auckland City Hospital
Dear SIRS I don’t like you...
Department of Emergency Medicine
Auckland City Hospital
Definitions Cont.
Department of Emergency Medicine
Auckland City Hospital
High Risk Patients
For Sepsis
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Post op / post procedure / post trauma
Post splenectomy (encapsulated organisms)
Cancer
Transplant / immune supressed
Alcoholic / Malnourished
For Dying
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Genetic predisposition (e.g. meningococcus)
Delayed appropriate antibiotics
Yeasts and Enterococcus
Site
For Both
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Cultural or religious impediment to treatment
Department of Emergency Medicine
Auckland City Hospital
Case 1
54yr Samoan male
24 hr Fever and delirium, Arrive 1300hr
Initial Obs
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HR 162, RR 30, sats 95% on 15l, BP 116/82,
GCS 13/15
History
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Migratory abdominal pain and fever 1/7
Examination
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GCS 15, CNS, CVS, RS, GIT normal
160kg
Department of Emergency Medicine
Auckland City Hospital
Differential Diagnosis
(this list is not exhaustive)
Pancreatitis
Ischeamic Gut
Hypovolaemic shock
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GI bleed / AAA rupture / ectopic / dehydration
Cardiogenic shock
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AMI / Myocarditis / Tamponade
PE
Toxic Shock Syndromes
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Staph Aureus
Group A Strep
Addisonian crisis (note relative adrenocorticoid insufficiency in
many septic patients)
Thyroid Storm
Toxidromes
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Anticholinergic / serotoninergic
Department of Emergency Medicine
Auckland City Hospital
Investigations
Basic
WBC
Platelets
Coags
Renal function
Glucose
Albumin
LFT
ABG
Department of Emergency Medicine
Auckland City Hospital
Specific ?Source
Urine
CxR
Blood Cultures x 2
LP
Aspirate
Biopsy
May all be normal early on!
Treatment
Specific
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Antibiotics
Empiric based on source
Know local pathogens
Use the RMO guidelines / pharmacy handbook for best
guess treatment
Ideal to get cultures 1st but do not delay antibiotics
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Surgery
Get the pus out! All of it!
Early definitive care will improve survival
Department of Emergency Medicine
Auckland City Hospital
Treatment
Supportive
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Oxygenate / Ventilate (6ml/kg)
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Volume
Will need more than ‘maintenance’ + replace losses with like
fluid
Colloid v Chrystalloid (SAFE trial awaited – know the
results!)
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Inotropes
Noradrenalin is inotrope of choice, dopamine next
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Early ICU referral
Department of Emergency Medicine
Auckland City Hospital
Treatment
Supportive
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Electrolyte homeostasis
THAM for pH <7.2 1-2mL / kg over 20min
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Address co-morbidities
ß-Blocker & reduced inotropy
DM / COAD
Alcoholism / malnutrition / steroids
Stop nephrotoxins (NSAIDs)
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Early ICU referral
Department of Emergency Medicine
Auckland City Hospital
Case 1
54yr Samoan male
Investigations
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FBC, U and E, BC, MSU
ABG
Treatment
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IV Fluids
3l 0.9% Saline in 1.5 hours
1l Gelofusin in 1.5hrs
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IDUC
Antibiotics
Gentamicin 320mg, Augmentin 1.2gm
Past History
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April 2003 Left ureteric stone, 6mm
Referred urology, discharge next day “GP FU” for US
Department of Emergency Medicine
Auckland City Hospital
Case 1
54yr Samoan male
Results
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Urine Dip: 500wbc, no nitirites, 200rbc
FBC: wcc 4.67, pmn 3.85 (0.47bands) plt 177
Coag: Inr 1.1, Aptt 26, fibrinogen >7g/L
U and E: Na 132, K 4.6, U 10.6, C 0.26
CRP 301.9
ABG: pH 7.36, po2 23, pco2 5.3, hco3 22, be -2.7
Lactate:
3.0
CXR
Department of Emergency Medicine
Auckland City Hospital
Case 1
54yr Samoan male
Progress 15:10 hours
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Urology referral (accepted)
DCCM referral (declined)
Renal imaging booked : CT 1 2
Progressively hypotensive
55mL urine over 7 hours
Declined all treatment
Department of Emergency Medicine
Auckland City Hospital
Case 2
59 Male
29/10
Back pain, lifting fridge
Temp 37.3, HR 60 BP 130/60
Tender lumbar area with slight reduction SLR / R leg power
PR normal
Rx Analgesia, mobilised, discharged home
1/11
Represents 1400
Was getting better then worse again on mobilising
Temp 35.8, HR 112 BP 150/80
Asleep when reviewed
Findings as above →Treated with analgesia, handed over
Kept overnight → Urine test done
Department of Emergency Medicine
Auckland City Hospital
Case 2
59 Male
Urine: Trace blood +ve nitrites
LFT:
“because patient thought he was
jaundiced”
Bili 23, GGT 167, ALP 157 (40-120)
AST 60 (< 40), ALT 72 (< 45)
U and E:
Na 131. K 3.1, U8.4, C0.09
FBC: Normal (lympho 0.88)
Reviewed: Mobilising
Discharged with GP Follow up urine
Department of Emergency Medicine
Auckland City Hospital
Case 2
59 Male
2/11/03 Self presented to White Cross
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Temp 38.8c, GP rang lab → Staph Aureus
Referred medical ?pyelonephritis ?Discitis
BC done
Progress
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S/B med reg, Rx Flucloxacillin, stop NSAID
Delirium / L elbow bursitis
MRI: 4/11/03 L2-3 discitis, L psoas abscess, epidural
collection - decided not for drainage
Discharge with ongoing PICC antibiotics 6 weeks
Department of Emergency Medicine
Auckland City Hospital
Local Susceptibilities
There are current hospital
recommendations based on local
susceptibilities and presumed site of
infection on the intranet – USE THEM!
Look under Pharmacy, antimicrobial
guidelines, best guess therapy
Department of Emergency Medicine
Auckland City Hospital
Department of Emergency Medicine
Amoxycillin
Nitrofurantoin
Norfloxacin
Cefuroxime
Ceftriaxone
Gentamicin
Aztreonam
/ Sulfamethoxazole
Clavulanic Acid
Trimethoprim
Auckland City Hospital
Case 1
54yr Samoan male
Microbiology results
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Urine WCC >1000: RCC 310 million/L Bacteria : Present
COLONY COUNT : 10 to 100 million/L CULTURE Mixed growth
predominantly:
(1) E. coli (1) (1) Amoxycillin R Cephalothin S Cefuroxime S
Trimethoprim R Gentamicin S Cotrimoxazole R Norfloxacin S
Amoxycillin/clav. S Nitrofurantoin S
PERIPHERAL BLOOD CULTURE
(1) E. coli (1) (1) Amoxycillin R Cephalothin S Cefuroxime S
Ceftriaxone S Ceftazidime S Aztreonam S Trimethoprim R
Gentamicin S Amikacin S Cotrimoxazole R Norfloxacin S
Ciprofloxacin S Amoxycillin/clav. S Ticarcillin/clav. S
Meropenem S Nitrofurantoin S
Department of Emergency Medicine
Auckland City Hospital
Trimethoprim
Tetracyclines
Erythromycin
Flucloxacillin
Gentamicin
Amoxycillin
Penicillin
Sulfamethoxazole
Department of Emergency Medicine
Auckland City Hospital
Case 2
59 Male
URINE MICROSCOPY WCC 170 RCC 30 Epithel. cells <10
million/L Bacteria Present Granular casts 2 million/L
CHEMISTRY Protein : Moderate amount
COLONY COUNT : > 100 million/L CULTURE (1)
Staphylococcus aureus (1) (1) Penicillin R Flucloxacillin S
Cotrimoxazole S Doxycycline S Nitrofurantoin S Trimethoprim S
PERIPHERAL BLOOD CULTURE (1) Staphylococcus
aureus (1) (1) Penicillin R Erythromycin S Flucloxacillin S
Doxycycline S
Department of Emergency Medicine
Auckland City Hospital
Metronidazole
Clindamycin
Augmentin
Department of Emergency Medicine
Auckland City Hospital
Department of Emergency Medicine
Auckland City Hospital
Amphotericin
Local Organisms 1999-2000
ED / AAU / DCCM Positive BC 18/12, n=428
80
Pathogens
70
60
E.Coli
S Aureus
S Pneumoniae
Viridans Strep
Klebsiella
N Men
S Pyo
E Cloacae
Number
50
40
30
20
10
Organsim
IL
st
yp
H
FL
U
KO
XY
AC
IS
P
PM
I
SA R
G
B
SF
SM
Department of Emergency Medicine
Auckland City Hospital
AS
B
EC
LO
SP
YO
PA
C
N
PA
E
ST R
AS
P
M
R
SA
vs
M
IC
S
P
KL
E
C B
O
RS
P
N
M
EN
E
PR U
O
PS
SA
PN
EC
C
SE
PI
N
S
0
Local Organisms
Approx 45-55% positive ED BC are skin
organism contaminants
Similar across the hospital
This is approx 5% all BC done
Always get at least 2 blood cultures
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Help sort out ?contaminants
Department of Emergency Medicine
Auckland City Hospital
Case 1
54yr Samoan male
Subsequently declared incompetent by
pyschiatry, then consented to treatment
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Nephrostomy 21:30
DCCM admission (3 days)
Noradrenalin
CPAP (OSA)
Creatinine 0.10
Discharged 2/12/03
Department of Emergency Medicine
Auckland City Hospital
Local Outcomes
Mortality from sepsis varies
(Age, co-morbidity, illness severity)
DCCM data Auckland Hospital
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5-15% for meningitis / brain abscess / pid
20-35% for pneumonia / uti / abdominal
45-50% for mediastinum / joints
Data varies from other hospitals
? Due to Policies of DCCM for example
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Early tracheostomy
Admission criteria
Department of Emergency Medicine
Auckland City Hospital
Novel Therapies
Steroids
JAMA. 2002 Aug 21;288(7):862-71
Many (>50%) septic patients have relative adrenocortical
insufficiency.
Physiological hydrocortisone improves mortality in this group
(63% → 53%, p=0.02 in this study, n=229)
Antiinflammatory
Department of Emergency Medicine
Auckland City Hospital
Novel Therapies
Activated Protein C (Drotrecogin α)
N Engl J Med. 2001 Mar 8;344(10):699-709
Antithrombotic, antiinflammatory, profibrinolytic
1690 patients, Mortality 30.8% →24.7% p<0.01
Increased bleeding 2% →3.5% p=0.06
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Caution in meningococcal sepsis / trauma / ICH / pregnant!
$17181 / patient
Consensus in NZ is restricted last resort use in selected ICU
patients
Department of Emergency Medicine
Auckland City Hospital
Novel Therapies
Tight glucose control with insulin
N Engl J Med. 2001 Nov 8;345(19):1359-67.
Mortality reduction 8→4.6% (p<0.04) all icu
patients
Biggest reductions in severe sepsis / long
stayers
Also reduced bacteraemic episodes / icu
neuropathy
Aim 4.4-6.1mmol/L
Department of Emergency Medicine
Auckland City Hospital
Novel Therapies
rBacteriocidal/Permeability-increasing
protein
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In neutrophil granules
Binds to and inactivates endotoxin
Lancet. 2000 Sep 16;356(9234):961-7.
393 Children with clinical meningococcaemia
Mortality 9.9% → 7.4% p=0.48
Amputations 7.4% → 3.6%, p=0.067
Better functional outcome 66.3% → 77.3% p=0.019
Department of Emergency Medicine
Auckland City Hospital
Novel Therapies
Summary
Reducing mortality in sepsis: new
directions Critical Care 2002, 6(Suppl
3):S1-S18
(http://ccforum.com/content/6/S3/S1 )
This is highly recommended reading, concise reviews of
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Low tidal volume ventilation
Early goal directed therapy
Drotrecogin alfa (activated)
Moderate dose corticosteroids
Tight control of blood sugar
Department of Emergency Medicine
Auckland City Hospital
Novel Therapies
NAC Crit. Care. Med. 2003 31 (11) 2574-78
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Nuclear factor-κB controls expression
inflammatory mediators
NAC inhibits NFKB in vitro
Pilot trial
20 patients, randomised
72 hrs NAC or placebo
IL-8 suppressed (may be implicated in lung injury)
Recommend larger human trials
Department of Emergency Medicine
Auckland City Hospital
Summary
Sepsis may be obvious or subtle early
There is a high mortality and morbidity
Have a high index of suspicion
Know local organisms / susceptibilities
Take appropriate cultures
Treat early and aggressively
Investigate early and aggressively
Refer early and aggressively
Be aware of new developments
Department of Emergency Medicine
Auckland City Hospital
Antimicrobial Therapy
http://ahsl85_gl/FormularyGuide/
Best Guess
Department of Emergency Medicine
Auckland City Hospital
More References
Streat S Orientation Lectures for Medical Staff DCCM
12/1/2004 – This hospital’s approach
Bone RC Chest 101: 1644, 1992 (Definitions)
Vincent JL Crit Care med 1997 25(2) 372-74 Dear SIRS
-editorial
Angus DC Crit Care med 2001 29 (suppl) 7 s109-s116 –
epidemiology
Klinzing S Crit Care med 2003 31 (11) 2626-50 –
inotropes
Department of Emergency Medicine
Auckland City Hospital