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Sepsis
Hippocrates (460-377 B.C.), the most famous
doctor in ancient Greece, was titled as Father
of Medicine, who used "sepsis" to describeputrefaction and a bad smell.
Ubi pus, ibi evacua-"Where there is pus, thereevacuate it"
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Inflammation
Calor Rubor Tumor Dolor Functio laesa
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Incidence of diseases in Germany
§ AIDS 17/100.000
§ Bowel-Ca 50/100.000
§ Mamma-Ca 110/100.000
§ Sepsis 300/100.000*
Deutsche Sepsisgesellschaft 2004
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Sepsis in United States
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Two or mor e of the f ollowing:
Temp >38°C or <36 °C
Hear t r ate > 90 bpm
Resp r ate > 20 bpm or PCO2 < 32 mm HgWBC >12 or < 4 Gpt/l
Early LAB Clues
Glucose > 7 mmol/l
Cr eatinine incr ease > 0.5 mg/dLINR > 1.5 or aPTT > 60s
Thrombocytopenia < 100,000
Hyper bilir ubinemia > 34 umol/l
Lactate level > 2mmol/L
Diagnosis SIRS
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Definitions and Ter ms
Sepsis
± SIRS plus systemic manifestations of infection
Severe sepsis
± Sepsis plus sepsis-induced or gan dysfunction or tissue
hypoper fusion (Eg Oligur ia, elevated lactate, shock)
Septic shock-- Sepsis induced hypotension defined as
SBP < 90 mm Hg or
>40 mm Hg drop f rom baseline not r elieved with fluids
MAP < 70 mm Hg
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Organ Dysfunction
CNS (Confusion)
Renal (ARF) Respiratory (ARDS)
Haematologic (DIC)
Metabolic (Acidosis)
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Source of Infection
Lungs (41%) Abdomen (32%)
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Urinary tract (11%) Wounds + Soft tissue (5%) Tubes+Drains (5%)
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Sepsis
Obtain 2 sets of blood cultures, and other
appropriate cultures (eg urine, sputum,
wounds).
Administer appropriate antibiotics
immediately after obtaining blood cultures.
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Empirical AB treatment
di/flucloxacillin 2 g IV, 4- to 6-hourly
PLUS
gentamicin 4 to 6 mg/kg IV, for 1 dose, then adjust
subsequent dose for renal function
Penicillin-allergy
cephalothin 2 g IV, 6-hourly OR
cephazolin 2 g IV, 8-hourly.
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Febrile neutropenic patients
ticarcillin+clavulanate 3+0.1 g IV, 6-hourly
PLUS
gentamicin 4 to 6 mg/kg daily OR
ceftazidime 2 g IV, 8-hourly
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Goals
Search for a source and control it ASAP
Drain any infected fluid
Debride infected tissueRemove infected devices
Recommendations
Administer antibiotics in the ED within 1 hour of sepsisdiagnosis (after culturing!!!)
Initial broad coverage tailored to the potential source
Consider resistance patterns in nursing home patients
and patients on prior antibiotics
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The Tarragona Strategy
Hit hard with a high dose of broad-spectrum antibiotic.
Get to the point: use antibiotics according to their
pharmacodynamic response.
Focus, focus, focus: de-escalate when it is possible, according
to microbiological findings and do not prolong antibiotic therapy
unnecessarily.
Listen to your hospital: tailor the antibiotic policy according
to regularly updated information on the resistance patterns of local pathogens.
Look at your patient: individualise the initial antibiotic
therapy on the basis of the patients comorbidities, intubation
period and previous antibiotic exposure.
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Each hour
without adequate
AB Rx incr eases
mor tality by
7.6%.
82%, if AB initiated within 30 minutes, after 1-2 hour s sur vival r ate: 77%,
after 5-6 hour s: 50%
Duration of hypotension before initiation of effective
antimicrobial therapy is the critical determinant of survival in
septic shock
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Antibiotics
CeftriaxoneGood, broad spectrum 3rd generation cephalosporin with activity against mostGram-neg other than P. aeruginosa. Activity vs. anaerobes is not wellestablished.
Timentin (ticarcillin+clavulanic acid) good broad spectrum activity against awide range of Gram-positive and Gram-negative aerobic and anaerobicbacteria, Pseudomonas
Gentamicin
Gram-neg, Pseudomonas, ototoxicity as well as nephrotoxicity, the tendency tounderdose & the need to monitor levels.
Azithromycin
atypical pneumonia, gram-pos
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Antibiotics
MeropenemVery similar to imipenem (favored drug for serious infections which requirea broad spectrum agent, active against almost all gram-pos and gram-negorganism). Probably less seizure potential.
Di/Flucloxacillin
Staphylocooci, gram pos cocci
Vancomycin
Is active against most gram-positive cocci and bacilli, including almost all S.
aureus and coagulase-negative staphylococcal strains that are resistant topenicillins and cephalosporins (MRSA). Oto-, nephrotoxicity
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Activated Protein C
Drotregonin alfa (Xigris)-modulation of the systemicinfection response, limits thrombin formation
represents the only specific therapeutic modality
apart from antibiotics that has been shown toimprove mortality in severe sepsis and septic shock.
Protein C is approved only for use in patients withsepsis who have the most severe organ
compromise and the highest likelihood of death.
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Volume Resuscitation
Early aggressive therapy that optimized cardiac preload,afterload, and contractility in patients with severe sepsis andseptic shock improved the likelihood of survi val.
Duringthe first 6 hrs of resuscitation, the goals of initial
resuscitation of sepsis-induced hypoperfusion should include:
CVP of 8 to 12 mm Hg,
MAP between 65 to 90 mm Hg central venous oxygen saturations > 70%.
Urine output 0.5mL.kg/hr
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Vasopressors
Dobutamine is useful in patients with myocardial depressionwith persistent low cardiac output following adequate fluidresuscitation.
A combination of dobutamine and norepinephrine, exertedbeneficial effect on gastrointestinal blood flow.
Norepinephrine may yield superior results clinically comparedwith dopamine.
Vasopressin, a potent vasoconstrictor, has an established rolein systemic arterial pressure maintenance.
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Australasian Practice
Noradrenaline is usually first agent used
Adrenaline also commonly used in resus
Dopamine seldom used any more (Renal dosedopamine does not work!!!)
Metaraminol (Aramine) commonly used
during anaesthesia for hypotension Dobutamine is used in low cardiac output states
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Intensive Insulin Therapy for Hyperglycemia
Insulin therapy reduced the rate of death frommultiple-organ failure among patients with
sepsis, regardless of whether they had ahistory of diabetes.
BSL 80 to 110 mg /dl (4.4 to 6.1 mmol per liter) but risk of hypoglycemia followed by
increased mortality BSL 120 to 160 mg/dl (6.7 to 8.9 mmol per
liter) same benefit?
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Corticosteroids
Administr ation of high doses of cor ticosteroids (e.g., 30
mg of methylpr ednisolone/kg BW) does not improve
sur vival among patients with sepsis and may wor senoutcomes by incr easing the f r equency of secondar y
infections.
Patients with sepsis who ar e extremely ill and have persistent shock r equir ing vasopr essor s and prolonged
mechanical ventilation may benefit f rom "physiologic"
doses of cor ticosteroids (Hydrocortisone 50-mg
intravenous bolus four times per day) andfludrocor tisone 50 er da
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Nutrition Support
Early je junal feeding may help maintain the normal bacterialmicroflora and the barrier function of intestines, thus,minimizing bacterial and endotoxin translocation. Incombination with pancreatitis, lack of enteral nutrition can
produce mucosal atrophy and increased permeability of intestinal barrier leading to failure of intestinal barrierfunction, which plays a pivotal role in bacterial translocation.In a recent study, approximately 3-6% of all patients with acutepancreatitis developed SIRS, sepsis, and MOF, likely as a resultof colonization and infection of the necrotic tissue. The rate of septic complications, including infected pancreatic necrosisand abscess, was lower in a group of patients treated withearly jejunal feeding compared with the conventionalparenteral nutrition.
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Hemodialysis
Acute renal failure in critically ill patients is
often associated with extra renal
complications that may instigate MOF and
high mortality. Renal replacement therapy
with intermittent hemodialysis is the current
standard, but an adequate dose of
maintenance hemodialysis is not currentlyknown.
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Potential Therapies for Sepsis
antibodies against complement-activation
product C5a decreased the frequency of
bacteremia, prevented apoptosis, and
improved survival
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Procalcitonin
PCT is not a better marker of bacterial
infection than CrP for adult emergency
department patients, but it is a useful markerof the severity of infection.
Normal <0,5 ng/ml Sepsis >2,0 ng/ml
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Age-specific incidence (per 1000 population) of
severe sepsis patients with and without cancer.
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Systemic Inflammator y Response Syndrom
Inflammatorische Parameter
Leukocytose (> 12000 /l)
Leukopenie (< 4000 /l)
Normale Leukozytenzahl mit > 10% unreifen
Formen im Differentialblutbild
CRP > 2 SD über Normwert
Procalcitonin (ProCT) > 2 SD über Normwert
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Initial choice of vasopressor
Noradrenaline
Via CVC
To maintain MAP > 65 mmHg
Adrenaline, phenylephrine, or vasopressin NOT first line (2C)
Adrenaline as first alternative agent when BP poorly
responsive
Low-dose dopamine for renal protection doesnt work
Insert an arterial catheter as soon as practical
Use dobutamine in patients with myocardial dysfunction
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Early goal-directed therapy (EGDT
Otero, R. M. et al. Chest 2006;130:1579-1595
Algorithm of EGDT
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Activated protein C
represents the only specific therapeutic
modality apart from antibiotics that has
been shown to improve mortality in severesepsis and septic shock. In contrast, recent
phase III trials of related therapies such as
antithrombin III and tissue factor pathway
inhibitor have failed to demonstrate
improved survival.
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Cor ticosteroids