ECC2- Sepsis

systemic inflammatory response due to an infection that may be d/t bacteremia, viremia, fungemia, or other causes.

• 1. vascular changes
• 2. leukocyte recruitment
• 3. leukocyte activation
• 4. termination

• Vasodilation 
• Interstitial edema

d/t histamine from mast cells, serotonin from platelets, and nitric oxide from endothelial cells

• modifications of starlings forces
• endothelial cell contraction
• endothelial cell death

oncotic pressure, hydrostatic pressure, vascular permeability.

• from the blood stream to the site of injury by:
• 1. margination (d/t blood stasis)
• 2. rolling and adhesion (adhesion molecules)
• 3. diapedesis
• 4. migration by chemotaxis (neutrophils then macrophages)

• Goal of inflammation- to remove source of breakdown and removal of damaged tissue and/or infectious agents by:
• arachidonic acid pathway--> prostaglandins/ leukotrienes
• oxidative burst and reactive oxygen species
• phagocytosis
• cytokine release

• prostaglandins, leukotrienes, platelet-activating factor
• vasodilation/ vasoconstriction (prostaglandins)
• chemotaxis (leukotrienes)
• thrombosis (PAF)
• **inflammation and coagulation are linked**

• reactive oxygen species
• lipid peroxidation and plasma membrane damage, DNA damage, amino acid damage, and induction of apoptosis

opsonization, engulfment of microbe, fuse with lysosome and digestion of microbial products

• removal of primary insult stops stimulation
• release anti-inflammatory cytokines
• switch to anti-inflammatory pathway

• eliminate the cause of the injury
• increase immune defenses
• balanced, controlled response

• systemic inflammatory response syndrome
• uncontrolled or excessive inflammatory response, causing normal tissue to be damaged due to excessive host response (rather than from the primary disease)

• local overflow of pro-inflammatory mediators into systemic circulation
• prolonged or severe inflammation eventually overwhelms the natural anti-inflammatory mechanisms

• Local: redness, pain, heat, swelling
• Systemic: tachypnea, tachycardia, temperature, WBC changes

• HR >150
• RR > 40
• Temp >103 or <99
• WBC >19 or <5
• **Must have 2 of these criteria + a disease process susceptible to induce SIRS**

• HR >200 or <140
• RR >40
• Temp >103 or <99
• WBC >20 or <5
• **Must have 3 of these criteria + a disease process susceptible to induce SIRS**

• non-infectious inflammatory diseases (meningitis, pancreatitis)
• Immune-mediated diseases (IMHA, IMPA)
• Neoplasia
• Trauma
• Surgery
• Infectious (sepsis)
• Snake venom
• Burns
• Heat stroke
• ischemia/ reperfusion
• Shock

Multiple Organ Dysfunction Syndrome: presence of altered organ dysfunction in an acutely ill patient such that homeostasis cannot be maintained without intervention

• not all inflamed/ infected patients have SIRS/ sepsis
• not all SIRS/ sepsis patients go into MODS and die
• all patients with MODS had SIRS/sepsis that was allowed to progress unnoticed
• the more organs dysfunctioning, the higher the mortality rate

• Stage 1: establishment of infection- sets up initial inflammation and cytokine release, body begins regulating
• Stage 2: preliminary systemic response- spill-over of mediators into systemic circulation; fever
• Stage 3: an overwhelming systemic response- excessive release of pro-inflammatory mediators; clinical syndrome of SIRS
• Stage 4: compensatory anti-inflammatory reaction- body attempts to down-reg pro-inflammatory mediators; if anti-inflamm reaction goes to far--> compensatory anti-inflammatory response syndrome (CARS)
• Stage 5: immunomodulatory failure-immune failure--> infection progresses, organ failure, death

the anti-inflammatory reaction goes too far, causing the immune system to become paralyzed and potentially allows the initial infection to spiral out of control

• pro-inflammatory cytokines
• 1. endothelial activation--> clotting cascade, microthrombosis--> ischemia, tissue hypoxia
• 2. direct injury by ROS and complement--> further loss of functional tissue
• 3. direct tissue damage from initial injury
• 4. edema formation d/t altered starling forces
• 5. microvascular dysfunction--> loss of tissue perfusion
• 6. apoptosis
• 7. impaired oxygen delivery from hypoperfusion, anemia, +/- hypoxemia

pro-coagulant

• not a lot of false negative, but lots of false positive
• important because we need to recognize SIRS in the early stages and not let it progress without treatment

• Shock treatment w/ early, aggressive fluid therapy
• Antibiotics early and aggressive (if infectious- sepsis)
• Monitoring
• Support of
• Organ function
• Nutrition early
• Pain

• [hyperdynamic findings]
• red MMs
• fast CRT
• bounding pulses
• decreased mental state
• warm extremities

• CVP 8-12mmHg
• MAP >65mmHg
• Urine output > 0.5mL/kg/hr
• S_cvO₂> 70%

• cardiac
• vascular
• renal- AKI
• lungs- ALI/ARDS
• coagulation- DIC
• GI
• immune system- CARS
• adrenal- CIRCA/ RAI

• hypovolemia, vasodilation, decreased inotropy, dysrrhythmia
• fluid therapy, vasopressors, positive inotropes, anti-arrhythmics

• clotting times
• platelet numbers
• FDPs/ D-Dimrs
• thromboelastogram
• Schistocytes
• serial measurements
• Treatments: treat primary cause of sepsis, +/- heparin for patients in prothrombotic phase, plasma for patients in bleeding phase

• urine cytology, oliguria/anuria (urine output <1mL/kg/hr), azotemia
• fluid therapy, mannitol, furosemide, hemodialysis, peritoneal dialysis

• SpO2, radiographs
• oxygen, fluid therapy, diuretics, mechanical ventilation