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Management of SepsisKarl Bolser DVM
SIRS Systemic Inflammatory Response Syndrome
MODS Multiple Organ Dysfunction Syndrome
Inflammatory MediatorsLipopolysaccharide Lipoteichoic acid Peptidoglycan Flagellin Mannan TNF⍺ IL-1 IL-6 Prekallikiein Bradykinin Cysteine-X-cysteine ligand 9 (CXCL-8;formerly IL-8)
SIRS
• Immunoparalysis
Compensatory Anti-inflammatory Response Syndrome
CARS
Definitions Prior to 2016Sepsis • 2 or more SIRS criteria with
suspected/known infection
Severe Sepsis • SIRS to infection • Organ dysfunction • hypoperfusion and/or
hypotension
Septic Shock • SIRS to infection • Hypotension refractory to
volume resuscitation
Definitions Prior to 2016Sepsis • 2 or more SIRS criteria with
suspected/known infection
Severe Sepsis • SIRS to infection • Organ dysfunction • hypoperfusion and/or
hypotension
Septic Shock • SIRS to infection • Hypotension refractory to
volume resuscitation
Sepsis after 2016
• Life-threatening organ dysfunction caused by a dysregulated host response to infection
DefinitionsSepsis • 2 or more SIRS criteria with
suspected/known infection
Severe Septis • SIRS to infection • Organ dysfunction • hypoperfusion and/or
hypotension
Septic Shock • SIRS to infection • Hypotension refractory to
volume resuscitation
Sepsis after 2016 • Life-threatening organ
dysfunction caused by a dysregulated host response to infection
c Shock
Severe
Proposed SIRS CriteriaDog Cat
Temperature (°F) ≥ 104 or ≤ 99 ≥ 104 or ≤ 100
Heart Rate (bpm) ≥ 140 ≥ 225 or ≤ 140
Respiratory Rate (bpm) > 20 ≥ 40
White Blood Cells(cells/µL)
≤ 5,000 or ≥ 16,000
≤ 5,000 or ≥ 19,000
+/- Bands (%) ≥ 3 ≥ 5
It takes 2 (or 3)
Potential Causes of Sepsis
• Gastroenteritis • Bite wounds • Pneumonia • Prostatitis/prostatic abscess • Peritonitis • Pyometra • Pyelonephritis • Pyothorax
https://www.cliniciansbrief.com/article/bite-wounds
Other Potential Signs of Sepsis
• Altered mentation • Hyperemic mucous membranes – or the opposite • Shortened or delayed CRT • Hyper or hypodynamic pulses • Petechia • Ecchymosis
”Normal” Inflammation – 1st reaction
Local arterioles • Rapid, inconsistent, transient vasoconstriction
https://www.google.com/imgres?imgurl=https%3A%2F%2Fpedsinreview.aappublications.org%2Fcontent%2Fpedsinreview%2F38%2F11%2F511%2FF4.large.jpg&imgrefurl=https%3A%2F%2Fpedsinreview.aappublications.org%2Fcontent%2F38%2F11%2F511&docid=mV6Q3PCQrqFWsM&tbnid=q2xxif0qw7PlfM%3A&vet=1&w=1280&h=960&client=firefox-b-1-d&bih=636&biw=1254&ved=0ahUKEwihvYGHg-ngAhVOKKwKHfVjBDIQ__EBCAM&iact=c&ictx=1
Rubor, Tumor, Calor, Dolor Redness, Swelling, Heat, Pain Celsus 25 BC – 50 AD
Cardinal Signs of Inflammation
Functio Laesa Loss of Function
Virchow 1821 - 1902
Vasodilation & Edema•Dilation of arterioles and capillaries • Increase blood flow
•Endothelial cell contraction (↑ cell gaps) • Increased permeability • Leakage of fluid and protein
• Increased viscosity of blood
•Aggregation of platelets • Increased adhesion of leukocytes
https://www.sdix.com/portfolio/red-blood-cells-abo/
• Dilute and Degrade • Toxins, foreign material
• Kill or Sequester • microbes, foreign material, necrotic tissue,
neoplastic cells
• Provide wound healing factors • Increase temperature
• Vasodilation • Inhibit replication of some microbes
• Restrict movement of appendages and joints to allow time for healing and repair
Benefits of Inflammation
Neutrophils• Kill or neutralize
• Microbes • Tumor cells • Foreign material
• Phagocytosis & fusion with lysosomes • Secretion of granules into exudate • Produce inflammatory mediators • Undergo apoptosis • NETs (Neutrophil Extracellular
Traps)
Neutrophils• Kill or neutralize
• Microbes • Tumor cells • Foreign material
• Phagocytosis & fusion with lysosomes • Secretion of granules into exudate • Produce inflammatory mediators • Undergo apoptosis • NETs (Neutrophil Extracellular
Traps)
Nitric Oxide
Production • Endothelium • Leukocytes - macrophages • Neurons
Ingested nitrate
•Vasodilation
•Decreased heart rate & contractility
•Decreases leukocyte adhesion
Hypotension
• Nitric Oxide • Increased/induced synthesis • Vasodilation
• Change in RMP • Lactic acidosis • K-ATP channels activated – more negative RMP • Voltage-gated calcium channels inactivated – decreased vascular
tone
• Pro-inflammatory cytokines • Breakdown tight junctions – fluid shifts between spaces
Increased Vascular Permeability Damaged Endothelial Glycocalyx
• Shields vascular walls from shear/stress of direct exposure to blood flow • Reduces nitric oxide production
• Retains protective enzymes and coagulation inhibition factors • Superoxide dismutase • Antithrombin • Protein C system
• Prevents leukocyte adhesion
Treatment• Fluids • Antibiotics • Glucose control • Nutrition • Eliminate the source
IV Fluids
Saline
Hyperchloridemia and Acidosis
• Increased cytokine production • Induced hypotension • Increased risk of AKI • Increased mortality
Fluid Boluses
• 10 ml/kg in 3 minutes – Dogs • 10ml/kg in 6 minutes – Cats and
puppies
11 pound cat = 500 ml/hr for 6 minutes = 50 ml
A More “Conservative” Approach - canine
Weight in Pounds X
10 .
ml to give over 20 minutes
66 pound dog • 660 ml = 1980ml/hr (20
min)
vs
• 300ml = 6000ml/hr (3 min)
…..and even more FLUIDS!!!
•Wait 5 minutes and reassess • If 2 -3 boluses • Colloid • 5 ml/kg over 5 minutes dog
• 2 ml/kg over 5 minutes cat
• Hypertonic saline
• If still hypotensive • vasopressors and/or inotropes
HypotensiveMAP < 60 – 65 mmHg Systolic < 90 mmHg
Poor Man’s DinaMap
Femoral pulse • BP ≥ 60 mmHg
Dorsal Pedal/Dorsal Metatarsal • BP ≥ 90 mmHg
Urine Output
• > 0.5 ml/kg/hr • Preferably > 1 ml/kg/hr
Lactate>4 mmol/L – give bolus of IVF
Dopamine CRIVasopressor with positive inotropic effect
1– 4 mcg/kg/min (dopaminergic) • enhance renal and mesenteric perfusion
5 – 10 mcg/kg/min (β-1 adrenergic) • increased myocardial contractility
10 – 15 mcg/kg/min (mixed α & β) >15 mcg/kg/min (α-1 adrenergic) • constriction of the renal arteries, thereby
potentially reducing renal perfusion and causing irreversible renal damage.
• Start at 5 mcg/kg/min • Maximum of 20 mcg/kg/min
http://vetmed.illinois.edu/CRIcalculator
http://www.vasg.org/blood_pressure_management.htm#
Others• Dobutamine • Ephedrine • Epinephrine • Norepinephrine • Etc.
Antibiotics
• Increase inflammation • Worsen AKI • Endotoxin release • Faster resolution of
inflammation and AKI • Usage correlated best with
survival
•Expect initial worsening of renal values
Antibiotics: When and Which Ones?• Mortality significantly increases for every hour of
delay 6 hours after diagnosis of septic shock • For every 1 hour delay of antimicrobials • Mortality increases 7.6%.
• Dickinson et al • 52.6% received appropriate therapy based on C&S
• 58.5% survived • 52.6% survival in those that received “inappropriate”
therapy
Antibiotics We Use• Unasyn (ampicillin sulbactam) • Enrofloxacin • E coli is frequently resistant
• Metronidazole
BUT
• Use something injectable (i.e. IV) – even aminoglycosides
Alterations in GlucoseHyperglycemia
• Increased cortisol (stress hyperglycemia) • Increased release of epinephrine,
norepinephrine, glucagon…. • Inhibition of insulin release due to pro-
inflammatory cytokines et al • Insulin resistance
Glucose
Increased production
Decreased cellular intake
Alterations in Glucose
Effects of Hyperglycemia
• Pro-inflammatory • Pro-thrombotic
Effects of Insulin
• Anti-inflammatory effects • Anti-thrombotic effects
Alterations in Glucose
Hypoglycemia
• Increased use • Both bacteria and leukocytes
• Depletion of glycogen • Decreased production
Other Causes
• Addison’s • Xylitol
Nutrition• NG and E Tubes • Intervene early
Septic Abdomen Treatment• Resect what you need to • Lavage • Lavage • Lavage • +/-drain
Abdominal Fluid Analysis Minimum
• PCV/TP • Need to be ≥ 5% before
considered hemorrhagic
• Cell Count • Hemocytometer is best *Machines may not be verified
• Cytology
www.badtaxidermy.com
What is it???
Classifying the Fluid• Transudate - clear • Protein (g/dl) <2.5 • Cell Count (cell/mcl) <1,500
• Modified Transudate – hazy to turbid • Protein (g/dl) 2.5 – 7.5 • Cell Count (cell/mcl) 1,000 – 7,000
• Exudate – opaque to turbid • Protein (g/dl) >3.0 • Cell Count (cell/mcl) >7,000
• Transudate Low Protein • Transudate High Protein • Exudate Nonseptic • Exudate Septic • Hemorrhagic • Lymphatic Loss
Classifying the Fluid• Transudate - clear • Protein (g/dl) <2.5 • Cell Count (cell/mcl) <1,500
• Modified Transudate – hazy to turbid • Protein (g/dl) 2.5 – 7.5 • Cell Count (cell/mcl) 1,000 – 7,000
• Exudate – opaque to turbid • Protein (g/dl) >3.0 • Cell Count (cell/mcl) >7,000
• Transudate Low Protein • Transudate High Protein • Exudate Nonseptic • Exudate Septic • Hemorrhagic • Lymphatic Loss
Pathologic Basis of Veterinary 6th Edition, Figure 3-3
Other Things to Think AboutUroabdomen? • Creatinine • Potassium
Bile Peritonitis? • Bilirubin
*Machines may not be verified
> 2 times peripheral blood
Suggestions of Sepsis
Glucose > 20 mg/dl difference
Lactate > 1.5 mmol/dl difference
*Polycythemia can cause a falsely low reading on some glucometers