Sepsis causes cellular injury via three mechanisms (tissue ischemia, cytoplasmic injury and altered apoptosis). Describe how it causes tissue ischemia:
- TNFa and IL-1 activate both coagulation and fibrinolysis which leads to microcirculatory lesions and disrupted blood flow.
- Neutrophils bind to endothelial cells and secrete reactive O2 species, endothelin, NO, platelet activating factor and lytic enzymes which damage endothelial cells and disrupt blood flow.
- RBCs become rigid
Sepsis causes cellular injury via three mechanisms (tissue ischemia, cytotoxic injury and altered apoptosis). Describe cytotoxic injury:
-TNFa and NO cause mitochondrial dysfunction which leads to cell death via histotoxic anemia. Even if there is oxygen present, the cell can’t use it.
Sepsis causes cellular injury via three mechanisms (tissue ischemia, cytoplasmic injury and altered apoptosis). Describe altered apoptosis:
- Proinflammatory cytokines delay apoptosis of dysfunctional cells, prolonging sepsis.
- Sepsis induces lymphatic and dendritic cell apoptosis which results in decreased clearance of invading microorganisms.
TNFa and IL-1 are the major cytokines in sepsis. What do they cause?
- Fever
- Hypotension
- Leukocytosis
- Induction of other proinflammatory mediators
- Simultaneous activation of coagulation and fibrinolysis
Causes of worsened hemodynamics in septic patients:
- Prostacyclin and NO secreted by endothelial cells cause vasodilation and loss of metabolic autoregulation.
- Venodilation decreases preload and CO.
- Arterial dilation causes decreased MAP and EOP, including decreased coronary perfusion.
- Microvasculature permeability leads to fluid extravasation.
- Impaired secretion of ADH
- Myocardial depressant factors
How does sepsis cause ARDS?
Neutrophil entrapment within the lung’s vast microcirculation initiates or amplifies injury to the alveolocapillary membrane which leads to microvascular permeability and leads to interstitial and pulmonary edema.
SIRS Criteria
2 of 4:
- RR > 20 or PaCO2 < 32
- Temp < 35 to > 38.3
- WBCs < 4,000 or > 12,000 or > 10% immature forms
- HR > 90 sinus
qSOFA is a predictive tool that calculates the risk of death from sepsis, not a diagnostic tool. What are it’s three components?
- RR > 22
- Altered mentation
- SBP < 100
- Score of one (3%), two (18%) and three (24%) = risk of mortality.
Define sepsis:
SIRS with an infection
Define severe sepsis:
Sepsis + organ dysfunction, but negative lactate.
Define MODS:
Progressive organ dysfunction such that homeostasis cannot be maintained without intervention.
List some conditions that could make a patient “immunocompromised.”
- Neoplasms
- Renal failure
- Hepatic failure
- AIDS
- Asplenism
- Immunosuprression medications
List some circumstances that would put a septic patient at even greater risk of death:
- Infection site is in lungs, GI tract or unk.
- ABx in the last 90 days
- Low platelet count
- Lactate > 4.0
- Hyperglycemia on admission
- Nosocomial, instead of community acquired pathogens
- Being old
- Hypocoagulability
Key markers to assess when querying MODS:
- P:F ratio (< 300)
- Platelet count (< 100)
- Serum total bilirubin (> 4mg/dL)
- Serum creatinine (increases of > 44)
- GCS
- Hypotension and vasopressor requirements
Common causes of non-infectious SIRS:
- Autoimmune disorders
- Burns
- Pancreatitis
- Vasculitis
- Thromboembolism
- Surgery
How does sepsis affect the microvasculature?
- Angiopathy -> Platelet consumption -> DIC
- Mitochondrial toxins -> Histotoxic anemia
- Fluid extravasation
- Vasoconstriction (late sign)
How does sepsis affect the macrovascularture?
- Arterial vasodilation -> Low MAP -> Decreased EOP/coronary perfusion
- Venodilation -> Pooling -> Decreased preload -> Decreased CO
- Myocardial depressant cytokines -> Decreased contractility
Simple equation that sepsis resuscitation can be pulled back to:
DO2 = CO x Arterial O2 content
List some common sites of infection and whether they’re gram positive or negative:
- Gram positive are often found on the skin and oral mucosa (cellulitis, endocarditis, meningitis , necrotizing fasciitis). Tx with 2g Ceftriaxone and 500mg Azithromycin, +/- Vancomycin.
- Gram negative are often found in the GI tract (bilary, peritonitis, UTI). Tx with 3.375g Pip/Tazo. If it smells, it’s gram negative.
Simple rule of thumb when distinguishing whether to use Ceftriaxone or Pip/Tazo:
- If it’s above the diaphragm, Ceftriaxone (2g)
- If it’s below the diaphragm, Pip/Tazo (3.375g)
What’s one lab value you can look at to determine if the sepsis is involved in the muscles and there’s possibly a component of necrotizing fasciitis (surgical disease).
CK
4 Principles of Sepsis Management:
- ) Source control
- ) Early and aggressive ABx
- ) Optimize DO2
- ) Ancillary therapies (steroids, glycemic control, albumin therapy, heparin)
To optimize DO2 in sepsis, what steps should you complete in order?
- ) Assess volume status and improve preload (20-30cc/kg). Look at passive leg raise, IVC, CVP trend, skin temp and response to fluid.
- ) Levophed, then vasopressin.
- ) If still cold peripherally, assess for septic cardiomyopathy (troponins, high CVP/low SvO2, ECG changes) and start Milrinone (high HR) dobutamine (low HR).
Well shit, you’re in refractory distributive shock (>50mcg/min of levophed). What do you do?
- Check for reversible causes (PTX, tamponade)
- Ensure right line, drug, concentration
- Reassess preload and give them fluid to squeeze
- Reassess source control
- Check for metabolic acidemia < 7.10, treat with NaHCO3
- Check for hypocalcemia <1.0 or hypoalbuminemia
- Is there too much sedation?
- Consider 50mg hydrocortisone for adrenal insufficiency
- Shit! Did you check for anaphylaxis?!
- All else fails, try methylene blue
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Term 156
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Shock Differential6
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Mech Vent and Anesthesia76
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Pharmacology71
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Transfusion Medicine39
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Radiology41
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Neuro152
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Genitourinary/Toxicology92
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Patient Assessment15
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CVS94
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Gastrointestinal55
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Trauma60
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Respiratory90
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Treatments53
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Sepsis42
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Special Populations27
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Endocrine/Integumentary21
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Environemental/CBNRE6
