Sepsis and Antimicrobials

clinical manifestation of an infection that results in systemic inflammatory response by the host

sepsis

constellation of clinical signs of systemic inflammation noted in response to infectious or noninfectious causes

systemic inflammatory response syndrome (SIRS)

persistent hypotension despite volume resuscitation associated with sepsis (or a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities substantially increase mortality)

septic shock

physiologic abnormalities of the endothelial, respiratory, renal, cardiovascular, hepatobiliary, coagulation, nervous, endocrine, and GI systems associated with systemic inflammation

Multiorgan dysfunction (MODS)

infection within the bloodstream

septicemia

systemic deactivation of the immune system tasked with restoring homeostasis from an inflammatory state

Compensatory and Inflammatory Response Syndrome (CARS)

Examples of PAMPs that trigger inflammation?

LPS

Lipoteichoic acid

Peptidoglycan

Bacterial DNA or RNA

Mannan

Examples of DAMPs that trigger inflammation?

Cell free DNA/RNA

Heat shock proteins

HMGB1

Hyaluronan

ATP

Histones

Heparan sulfate

What cytokines are released with systemic inflammatory response syndrome (SIRS)?

TNF-a

IL-1B

IL-6

IL-8

INF-y

What are the consequences of pro-inflammatory cytokines release with systemic inflammatory response syndrome (SIRS)?

Marked inflammation

Coagulation

Vasodilation

What cytokines are released with Compensatory and Inflammatory Response Syndrome (CARS)?

IL-4

IL-10

IL-13

TGF-B

What are the consequences of pro-inflammatory cytokines release with Compensatory and Inflammatory Response Syndrome (CARS)?

Immunosuppression

Systemic effects of inflammatory cytokine release?

Fever

Vasodilation

Systolic dysfunction

Glycocalyx destruction

Fluid and WBC extravasation

Acute phase protein production

DIC

Critical illness-related corticosteroid insufficiency (CIRCI)

Sepsis can cause what forms of shock?

Distributive

Hypovolemic

Cardiogenic

Metabolic

QAR to dull

Normal to febrile

Tachycardic

Tachypneic

Normal to hyperemic mucous membranes

Normal to hyperdynamic pulse

CRT<1sec

Normal to hypertensive BP

Normal extremity temperature

Is this pt in compensatory/hyperdynamic or decompensatory/hypodynamic shock?

compensatory/hyperdynamic

1 multiple choice option

Obtunded

Hypothermic

Tachycardic or bradycardic

Tachypneic

Pale mucous membranes

Weak to absent pulse

CRT >2sec

Hypotensive

Cold extremity temperature

Is this pt in compensatory/hyperdynamic or decompensatory/hypodynamic shock?

decompensatory/hypodynamic

1 multiple choice option

Most common sources for sepsis?

-Septic peritonitis

-Pyothorax

-Pneumonia

-Urogenital sepsis

-Septicemia

-Endocarditis

-Dermal sepsis

-Hepatobiliary sepsis

What are the different criteria used to recognize sepsis?

1. Systemic inflammatory response syndrome criteria

2. Sequential organ failure assessment score (SOFA)

3. qSOFA

What are the qSOFA criteria that raise suspicion of sepsis and indicate further diagnostics/exploration?

Respiratory rate >22bpm

Altered mentation

BP <100mmHg

Biomarkers for sepsis?

-Lactate

-Glucose

-Leukogram (neutrophilia, leukopenia, bands)

-Cell free DNA

-Procalcitonin

-C-reactive protein

-Cytokines

Tier 1 diagnostics for sepsis?

BP

ECG

Pulse ox

Venous blood gas

Blood smear

POCUS

Tier 2 diagnostics for sepsis?

Biochemistry

CBC

UA

Coag testing

Rads

Tier 3 diagnostics for sepsis?

Abdominal U/S

CT

Echo

Ex-lap

Methods of antimicrobial testing for suspect sepsis patients?

-Blood culture

-Urine culture

-Joint effusion culture

-Wound culture

-Cavitary effusion

-Respiratory sampling (trach wash or PCR etc.)

-PCR

-Serology

What is included in effusion analysis?

Cytology

Glucose level

Lactate level

a glucose that is ? in effusion compared to blood indicates sepsis

20mg/dL lower

3 multiple choice options

a lactate that is ? in effusion compared to blood indicates sepsis

2mmol/L higher

3 multiple choice options

How do we treat sepsis?

-Isotonic Crystalloids

-Colloids for those with large fluid volumes

-+/- Synthetic colloids

-Restrictive use of blood products

-Vasopressives

-Abx

-O2

-Hydrocortisone for CIRCI after they are vasopressor dependent

-GI support

-Early enteral feeding

-Dextrose PRN

-Pain meds PRN

-+/- antithrombotics

-address the source

blood volume that creates a positive pressure within the vessel (arterial)

stressed volume

1 multiple choice option

blood volume that fills the vascular bed without creating pressure (venous)

unstressed volume

1 multiple choice option

first line vasopressor agent for sepsis tx?

norepinephrine

second line vasopressor agent for sepsis tx?

vasopressin

third line vasopressor agent for sepsis tx?

epinephrine

first line agent for septic cardiomyopathy tx in dogs?

Dobutamine

first line agent for septic cardiomyopathy tx in cats?

Dopamine

alternative agents for septic cardiomyopathy tx in dogs and cats?

Epinephrine

Pimobendan

therapy used for non-life threatening conditions characterized by a narrow antibiotic selection that covers the most likely pathogen which can be changed based on culture and sensitivity testing

Escalation therapy

1 multiple choice option

therapy used for life threatening conditions (e.g. pneumonia, sepsis) characterized by an empiric, broad spectrum antibiotic selection that will be narrowed down based on culture and sensitivity testing

De-escalation therapy

1 multiple choice option

If shock is present and sepsis is definite or probable, when should they recieve Abx?

within 1 hour

If shock is present and sepsis is possible, when should they receive Abx?

within 1 hour

If shock is not present and sepsis is definite or probable, when should they receive Abx ?

within 1 hour

If shock is not present and sepsis is possible, when should they receive Abx?

Within 3 hours

What is the biggest risk factor for developing multi-drug resistant infection?

Abx within the last 3 months

Risk factors for developing multi-drug resistant infection following Abx?

-Recent Abx

-Hospitalization > 5 days

-Environment with lots of resistance

-Immunosuppresion

-Health-care related infection

-GI translocation

-Invasive procedures

-Indwelling catheters

Antibiotic tissue penetration is dependent on

-Perfusion

-Permeability

-Urine vs. renal tissue target

-Whether agent is intracellular

-If anaerobic or acidic environment

-Hemoglobin interaction

Time-dependent antibiotics work best when given

multiple times a day or as a CRI

Concentration-dependent antibiotics work best when given

at high doses

What are the different methods of sepsis source control?

1. Prompt surgical intervention

2. Thoracic tube placement

3. Point of care debridement

Septic peritonitis general prognosis?

50/50

Pneumonia, pyelonephritis, and pyothorax generally have a ? prognosis for survival

good

What forms of sepsis have the lowest chance of survival?

Endocarditis

Necrotizing fascitis

how many SIRS criteria need to be met to diagnose SIRS in dogs?

2

how many SIRS criteria need to be met to diagnose SIRS in cats?

3

SIRS + infection indicate

sepsis

What are the different parameters for the SIRS criteria?

Temperature

HR

RR

WBC (thou/ul)

Bands %

temperature SIRS criteria for dogs?

<100.6 or >102.6

HR SIRS criteria for dogs?

>120

RR SIRS criteria for dogs?

>20

WBC SIRS criteria for dogs?

<6 or >16

Bands % SIRS criteria for dogs?

>3

temperature SIRS criteria for cats?

<100 or >103.5

HR SIRS criteria for cats?

<140 or >225

RR SIRS criteria for cats?

>40

WBC SIRS criteria for cats?

<5 or >19.5

Bands % SIRS criteria for cats?

>5