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 90
Respiratory Rate >20 or PaCO2 12 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 2mmol/L
Oliguria 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
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
Post op / post procedure / post trauma
Post splenectomy (encapsulated organisms)
Cancer
Transplant / immune supressed
Alcoholic / Malnourished
For Dying
Genetic predisposition (e.g. meningococcus)
Delayed appropriate antibiotics
Yeasts and Enterococcus
Site
For Both
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
HR 162, RR 30, sats 95% on 15l, BP 116/82,
GCS 13/15
History
Migratory abdominal pain and fever 1/7
Examination
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
GI bleed / AAA rupture / ectopic / dehydration
Cardiogenic shock
AMI / Myocarditis / Tamponade
PE
Toxic Shock Syndromes
Staph Aureus
Group A Strep
Addisonian crisis (note relative adrenocorticoid insufficiency in
many septic patients)
Thyroid Storm
Toxidromes
Anticholinergic / serotoninergic
Department of Emergency Medicine
Auckland City Hospital
Investigations
Basic Specific ?Source
WBC Urine
Platelets CxR
Coags Blood Cultures x 2
Renal function LP
Glucose Aspirate
Albumin Biopsy
LFT
ABG May all be normal early on!
Department of Emergency Medicine
Auckland City Hospital
Treatment
Specific
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
Surgery
Get the pus out! All of it!
Early definitive care will improve survival
Department of Emergency Medicine
Auckland City Hospital
Treatment
Supportive
Oxygenate / Ventilate (6ml/kg)
Volume
Will need more than ‘maintenance’ + replace losses with like
fluid
Colloid v Chrystalloid (SAFE trial awaited – know the
results!)
Inotropes
Noradrenalin is inotrope of choice, dopamine next
Early ICU referral
Department of Emergency Medicine
Auckland City Hospital
Treatment
Supportive
Electrolyte homeostasis
THAM for pH 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
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 (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
Flucloxacillin
Gentamicin
Amoxycillin
Penicillin
Erythromycin
Sulfamethoxazole
Department of Emergency Medicine
Auckland City Hospital
Case 2
59 Male
URINE MICROSCOPY WCC 170 RCC 30 Epithel. cells 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
Clindamycin
Augmentin
Metronidazole
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
70 Pathogens
60
E.Coli
50 S Aureus
S Pneumoniae
Number
40 Viridans Strep
Klebsiella
30 N Men
S Pyo
20 E Cloacae
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Department of Emergency Medicine
Auckland City Hospital Organsim
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
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
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
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
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
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
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
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
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