Flashcards in sepsis Deck (20):
1. Describe the cardinal signs and symptoms of sepsis, severe sepsis septic shock and multiple organ dysfunction syndrome (MODS).
Sepsis: Temp (>38, 90, RR >20, PaCO2 >32, organ dysfunction plus documented evidence of infection, . Severe septic shock: sepsis sx plus BP 2 organ dysfunctions requiring intervention.
What causes organ failure in sepsis
inflammation and oxidant stress.
Describe organ dysfunction seen in sepsis
Hyperbilirubinemia, thrombocytopenia, paralytic ileus, coag abnormalities (INR >1.5), Increased creatinine, oliguria, PaO2 : FiO2 <300.
Hypoperfusion variables in sepsis
hyperlactatemia, decreased capillary refill
Describe the progression of sepsis and molecular mediators
Primary sepsis mediators are IL-1, TNFa, ROS, RNS, lipids > secondary mediators are NO, PAF, PG, LT, IL, kinins > vicious cycle of hypoperfusion, ischemia, microcirculatory shunts and acidosis > vasodilation, capillary leak, endothelial damage, microvascular obstruction and myocardial depression lead to multiple organ death > death
Common causes of sepsis
Usually gram negative bacteria, followed by gram positive. Most common initial site of infection is respiratory, but highest mortality results when intial infection is bacteremia
Acute phase response to infection
PAMPs (LPS or peptidoglycan) bind to intracellular TLRs > release of NF-kB and transfer to nucleus > trxn of cytokines (TNFa, IL-1B, IL-10) > activation and binding of macrophage > macrophage releases prostaglandins, leukotrienes, proteases and oxidants. Cytokines cause vasodilation and endothelial activation, leukocyte recruitment/activation, coagulation and NET formation
describe vascular endothelium during sepsis
NETs with trapped platelets lead to thrombosis and tissue hypoperfusion. This, plus vasodilation, decreased blood pressure and decreased RBC deformability lead to decreased tissue oxygenation and organ failure
Energy metabolism in sepsis
Mitochondrial dysoxia or cytopathic hypoxia: oxygen utilization by mitochondria is dysfunction, but oxygen delivery is preserved. This causes impaired pyruvate delivery, inhibition of Krebs cycle or ETC. Fail to maintain mitochondrial membrane gradient and uncoupling of ATP synthase. Mitochondrial damage also releases DAMPS, leading to further inflammation
treatment of early vs late sepsis
early: modulate immune response to prevent cytokine release. Late: block apoptosis or enhance immune function since death is usually due to infection (primary or secondary)
Bundled therapies for sepsis
Resusciation bundle: start immediately and complete within 3 or 6 hrs. after recognition of sepsis. Broad spectrum Abx -1hr > IV saline within for first 2 hrs (add albumin) > normalize serum lactate > vasopressors (NE, add epi. DOPA only in selected. vasopressin possible) > Get to quantitative resuscitation targets. 24 hr: Mx bundle.
How Quickly Should Antibiotics Be Given After Severe Sepsis is Recognized?
Mortality increases by 7.5% per hour beyond the first hour of shock. Start IV Abs within first hour of recognition of septic shock and severe sepsis without septic shock.
How to choose Abx for sepsis
If unknown source, cover empirically for MRSA, double cover for resistant gram negatives. If pt gets septic while on Abx for >3-5 days, assume new pathogen is resistant and start 2 new gram negative agents.
How to diagnose the cause of sepsis rapidly
Molecular methods: qPCR, molecular fingerprinting, riboleukogram. Immunodetection and automated microscopy
describe automated microscopy
Bacteria enter flowcell and electrical field forces cells to surface. Bacteria grow on surface and can be viewed with microscope. Susceptibility testing is avilable in multichannel flow cell.
fluid therapy in sepsis
Use crystalloids (portion may be albumin equivalent). Albumin should be added for initial fluid resuscitation. Avoid HES
lactate in sepsis
Marker of tissue hypoxia and disease severity. Elevated lactate during initial and final phases of shock associated with higher mortality.
lactate treatment goal in sepsis
In patients with blood lactate concentration >4 mmol/L, we suggest that a decrease of lactate
by 10% or more within 6 hours may be targeted along with SvO2/ScvO2
Activated Protein C treatment
Inactivation of coagulation, thrombin production and PAR-1 cleavage. Inhibits transendothelial PMN migration. Blocks LPS-treated monocyte NFkB mediated TNFa production