Sepsis

Dr M. Kothalawela Infection -2 2009/10 batch

Objective
Understanding sepsis pathogenesis and role of cytokines in genesis of sepsis Detection of sepsis Sepsis markers Sepsis treatment Early aggressive AB therapy Outcome of sepsis and Prevention Guiding therapy using markers New trends POCT and NAT Summary 14/05/2013

How deadly is sepsis, comparison with acute MI, Lung, Colon and Breast Cancer Mortality in US

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In Sri Lanka
Burden of disease; masked due to given undue attention to NCDs ?

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Understanding Sepsis
Sepsis is not a specific disease But, a continuum of events triggered by the bodys inflammatory immune responses to a
bacterial, viral, fungal, or parasitic infection.
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Why People die of sepsis

INSULT INFLAMMATORY PROCES Renal

TISSUE INJURY

Cardiac Hepatic

ORGAN DAMAGE

ORGAN DISFUNCTION

Heam Pulmonary GI

DEATH
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ORGAN FAILURE

Cerebral

Pathogenesis
Sepsis is a manifestation of release of , cytokines in a sequential manner - cytokine cascade.

Cascade initiation with the production of TNF-a and IL- 1 (proximal cytokines) TNF-a and IL- 1 Responsible for most of the patho-physiologic process in sepsis
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TNF-a and IL- 1

TNF-a and IL- 1 - mediate directly or indirectly the hemodynamic and inflammatory changes characteristic of sepsis

TNF and IL-1 initiate a pro-inflammatory cascade, production of pro-inflammatory cytokines....

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IL-6, interferon (IFN)-g, IL-12, and And various chemokines

 These cytokines are necessary for normal function of the immune systems But, un-cordinated response of pro-inflammatory cytokines leads to sepsis cascade leading to

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Endothelial damage, immune cell activation, tissue hypoxia, hemodynamic instability etc

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The two phases of sepsisan early pro-inflammatory phase follows onto a later antiinflammatory phase.

Webster N R , Galley H F Br. J. Anaesth. 2009;103:70-81

The Author [2009]. Published by Oxford University Press on behalf of The Board of Directors of 14/05/2013 the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Detection of Sepsis
First noticeable change occur in molecular level Production of cytokines Then cellular changes take place (Slightly later than molecular changes) Noticeable increase of bio-markers

Clinical Signs of sepsis occur late (Symptoms of SIRS secondary to confirmed infective cause)
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Sepsis Clock

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Sepsis Treatment
Sepsis is a medical emergency. Sepsis need to be treated quickly and efficiently as possible and as soon as it has been identified. Clinical Features- Late Bio Markers- Early
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Sepsis Treatment
Antibiotics broad-spectrum Intravenous Ensure rapid action and rapid distribution to the target Risk of death from sepsis increases by 7.6% with every hour that passes before treatment begins
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Risk of death by 7.6% with every hour passes before commencing of appropriate therapy

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Appropriate Antimicrobial Treatment

Two-fold increase in mortality with inappropriate antimicrobial therapy Statistically significant increase in mortality with each hour from the onset of septic shock.

During First encounter initiate empiric antibiotics

Choice of antibiotics - guided by the knowledge of most common sites of infection and the most common infecting organisms
Most common site Lungs, Abdomen, GUT, Soft Tissue, Unknown Common pathogens Gram Positives more than Gram Negatives Most common Gram Positives Staph and Pneumococcus Most Common Gram Negatives- Escherichia coli, Klebsiella spp., Pseudomonas spp., and Enterobacter spp. Fungi approximately 6%

Samples for blood cultures should be taken from a per-cutaneous site and from any intravascular catheters. 14/05/2013

Over the years Gram Positives have overtaken Gram Negatives

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Site of Infection

Microorganisms

Therapeutic Choices

Streptococcus pneumoniae, Community-acquired Haemophilus influenzae, Third-generation cephalosporin with macrolide pneumonia Legionella pneumophila, or respiratory quinolone Mycoplasma pneumoniae S. pneumoniae, H. Early hospitalinfluenzae, L. pneumophila, Ceftriaxone, respiratory quinolone or ampicillinacquired pneumonia M. pneumonia; sulbactam, or ertapenem (<5 days) nonresistant gram-negative rods Pseudomonas aeruginosa, Klebsiella spp., Late hospitalAcinetobacter spp., acquired pneumonia methicillin-resistant Staphylococcus aureus Intra-abdominal infections Antipseudomonal cephalosporin or carbapenem, or antipseudomonal beta-lactam or beta-lactamase inhibitor, plus linezolid or vancomycin

Third-generation cephalosporin with Enteric gram-negative rods metronidazole, or beta-lactam or betaand anaerobes lactamase inhibitor, or carbapenem or moxifloxacin

Urinary tract infections

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Gram-negative rods; Enterococcus spp.

Extended-spectrum beta-lactam or aztreonam, with or without an aminoglycoside; ampicillin or vancomycin if Enterococcus is present

Source Control of Infection

Adequate source control of infection is as important as appropriate antimicrobial therapy in severe sepsis. Source control includes
removal of infected foreign bodies,
urinary catheters, intravascular catheters, peritoneal dialysis cannulas, prosthetic joints, vascular grafts, and mechanical valves. JJ shunts etc

Incision and drainage of abscesses

cutaneous abscesses, open or per-cutaneous drainage of intra-abdominal abscesses

For necrotizing fasciitis, Rapid and early surgical intervention

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Objective of source control

Reduction bacterial/fungal density at sight included removal of biofilms Facilitate antibiotic entry to the areas and early recovery

Prevent overwhelming cytokine activity

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Other Modalities
Fluid Resuscitation Optimizing Tissue Oxygenation Vasopressor Treatment Xigiris etc

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Outcomes
Although the incidence of severe sepsis is increasing, mortality rates continue to decrease. A recent study in a sepsis cohort, age was found to be an independent risk factor for death by sepsis mortality rates > 65y 27.7% < 65 17.7% An increasing number of older survivors of sepsis require skilled nursing facilities
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Prevention
Efforts to decrease the incidence of this infection of pneumonia
Vaccinate susceptible individuals against
influenza, H. influenzae, and S. pneumoniae.

Additionally, asplenic patients should receive vaccination against N. meningitidis The incidence of intravascular catheter-related blood stream infections can be reduced by Intra venous catheter bundle and exist site chlorhexidine applications Cases of VAP can be by maintaining ventilator patients semirecumbent at a 45-degree to prevent aspiration

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