Sepsis Flashcards
What is sepsis?
It is a dysregulated systemic response of the immune system. Normally, the inflammatory and coagulation response is localised to the infection site but in sepsis it is rapid and widespread and overwhelms the whole body which can lead to organ damage and even death.
What infections can cause sepsis?
Most commonly bacterial infections but fungal, parasitic and viral infections can also cause it. The infection can originate from anywhere and can cause damage to any system of the body.
Do patients fully recover from sepsis?
No, they can have secondary infections, chronic critical illness or post-sepsis syndrome
How does sepsis lead to immunosuppression?
By decreasing number of T cells as result of apoptosis, decreased production of cytokines (IL-6 and TNFa) in response to endotoxin. Also, neutrophils express fewer chemokine receptors which leads to dysfunctional chemotaxis.
What is sepsis characterised by?
- cytokines (IL-6, IL-1, TNFa)
- DAMPs
- Dysregulated anti-inflammatory action
- Complement activation
- Coagulopathy
- Loss of vascular integrity (apoptosis, VEGF, ANG-1)
- Excessive vasodilation
- Micro-thrombus formation compromising blood supply leading to tissue necrosis
- Organ damage
Who is at risk of sepsis?
- Patients with positive blood cultures
- AIDS, renal or liver failure patients
- Very young or elderly
- Alcohol and drug users
- Severe vitamin D deficiency
What is the treatment for sepsis?
- Early antibiotic therapy
- Fluids
- Monitoring
- Organ support
- Vasoactive agents
What would characterise a good immunotherapy for sepsis?
- Should do as little damage to immune function as possible
- Should avoid inflammatory rebound
- Should decrease the excessive but retain moderate inflammation to regain normally functioning immune response
What therapies failed in sepsis?
- Corticosteroids
- Anti-endotoxin antibodies
- TNF antagonists
- Ibuprofen
Why did these therapies fail?
- Poor PK testing in sepsis patients
- Timing of intervention
- Patient population is very heterogenous
- Because of complexity of sepsis single agent therapies are inadequate and require combination of several agents
What shows efficacy in sepsis?
- Tocilizumab (anti-IL-6)
- Early aggressive fluid resuscitation
- Antibiotics early
- Dopamine
- Vasopressin
- Norepinephrine
What are possible future directions in treatment of sepsis?
- GM-CSF
- IFN-y
- Mesenchymal stem cells
- Immunoglobulins
- Thymosin alpha
- anti-PD-1
