Sepsis And Septic Shock

Front 1

Sepsis epidemiology:

Back 1

*600-750,000 pt/yr
*100-200,000 deaths/yr
*17 Billion USD/yr

Front 2

Increase in sepsis rates in past few decades:

Back 2

*21 yr study: 10 million severe sepsis pt-750 million hospital discharges-NHDS in USA.
*More likely to develop in males.

Front 3

Incidence of Severe Sepsis by Age:

Back 3

Front 4

The changing microbiology of severe sepsis:
GPB, GNB, Fungi:

Back 4

*fungi mainly candida

Front 5

∆ in sepsis mortality rates in past 45 years:

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*due to better care in ICU.

Front 6

Definition of sepsis/continuum:

Back 6

*SIRS=just sick
*severe sepsis= inflammatory response has become badly damaging to yourself
*Septic shock = hypotension, severe

Front 7

Proposed Definitions of--
Infection:
Sepsis:
Septic Shock:

Back 7

*Infection: interaction with a microorganism that induces a local or systemic host response (old term-sepsis); if microbe induces no host response=colonization

*Sepsis: A deleterious host response to infection resulting in organ dysfunction remote from the site of infection (old term was "severe sepsis")

*Septic Shock: sepsis complicated by diffuse microvascular dysfunction causing hypotension not responsive to simple fluid challenge (usually accompanied by tissue hyoperfusion and multi-organ dysfunction)

Front 8

The pathobiology of fever:

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OVLT= organum vasculosum of the lamina terminalis

Front 9

Effect of fever on sepsis prognosis:

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*higher fever response means better survival from sepsis
*Determined by mitoDNA
*Northern Europeans are protected; somehow

Front 10

The Adaptive Value and the Perils of the Febrile Response:

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*Favorable Attributes
-Bactericidal to some pathogens
-Heat Shock Proteins, APR
-Iron stress for pathogens
-Increases cardiac output
-Increases PMN chemotaxis, phagocytosis, and B cell antibody responses

*Detrimental Effects
-Increases caloric needs
-Increased myocardial work
-Somatic tissue catabolism, cell turnover
-Febrile seizures, denatures proteins
-Increased fluid losses

Front 11

Should you treat fever?

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*In general-it's better not to treat fever in an infected patient; fever is a biomarker for successful intervention.

Front 12

Is there value to fever if you're not infected?
What about hypothermia?

Back 12

*No
*No- you should be more concerned about a hypothermic patient.

Front 13

Pathophys of septic shock:

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*Infection and Damage from inflammation look the same.

Front 14

What's the initiating cause of sepsis?
What the outcome determinant?

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*The pathogen is the initiating cause of sepsis
*But the host response determines outcome

Front 15

Different kinds of TLRs and what they recognize:

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*Lots of locations
*Lots of things they bind
*TLR2 --> gram negs
*TLR1 --> gram pos
*NOD1 and NOD2

Front 16

Describe damage in the microcirculation due to inflammation:

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Front 17

Why is it bad to stay in prolonged septic shock?

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*“The longer you’re in shock the less likely you will get out of shock”
*Adrenergic receptor down regulation following prolonged and repeated stimulation
*Massive release of nitric oxide via iNOS and eNOS synthesis
-vascular smooth muscle relaxation
-Oxidant stress, peroxynitrite production-apoptosis
-Insensitivity to C’AMP-mediated vasoconstriction
*Myocardial depression
-“MDF” (TNF, IL-1, IL-6, NO): ß3 receptor availability
*Vasopressin deficiency-V1 receptors up regulated
*Microvascular dysfunction, microthrombi

Front 18

Diagnosis of Sepsis:

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*No single lab test, clinical finding or hemodynamic event is diagnostic for sepsis
*Clinical Diagnosis of an invasive infection (with or without bloodstream invasion) + a deleterious host response - fever (or hypothermia), leukocytosis (or neutropenia), tissue hypoperfusion with or without systemic hypotension
*multiorgan involvement- DIC, AKI, ARDS, CNS dysfunction, Lactic acidosis, hepatic dysfunction
*Shock- fluid non-responsive hypotension (BP<90/60) with early hyperdynamic cardiovascular response (high CO, normal Lt Atrial filling pressure, Low systemic vascular resistance)

Front 19

Treatment of Severe Sepsis:

Back 19

*Standard therapy
-Early recognition and intervention
-Early fluid resuscitation, followed by restricted fluids
-Bactericidal antibiotics
-Treat the focal infection
-Supportive care

*Newer treatments of sepsis
-Intensive insulin therapy
-Stress dose steroids for relative adrenal insufficiency
-Hemofiltration and plasmaphoresis
-Low tidal volume ventilation
-Immunomodulators, maybe

Front 20

Describe the Golden 6 hours in sepsis treatment:

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Front 21

Importance of early antibiotics in sepsis:

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Front 22

What should fluid treatment be like in the second 24 hrs of sepsis treatment?

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*keep them on the dry side after first 24 hrs

Front 23

Effects of glucose control in sepsis treatment:

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-Studies have gone both ways.
-High blood sugar probably okay unless it's extremely high.

Front 24

VENTILATION WITH LOWER TIDAL VOLUMES COMPARED WITH TRADITIONAL TIDAL VOLUMES FOR ACUTE LUNG INJURY AND ARDS:

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*Use low stretch ventilation*

Front 25

Effects of activated PRO C?

Back 25

*None. Don't use it.

Front 26

Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock:

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-unclear.
-effects of steroids are inconclusive.

Front 27

Prognostic factors in septic patients:

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*Before onset of sepsis
-Severity of underlying disease
-Age
-Gender (males do worse)
-Genetic polymorphisms
-Status of Immune defenses

*After onset of sepsis
-APACHE II
-Need for ventilator
-Multiorgan failure
-Polymicrobial bacteremia
-Pseudomonas, candida, enterococcal bacteremia
-Early antibiotics, ? euglycemia, optimal fluids, low TV ventilation, ? Stress-dose steroids? albumin?

Front 28

Current overall mortality from sepsis:

Back 28

Current overall mortality 25-35% severe sepsis-40-45% for septic shock managed in the ICU.