Sepsis

Question 1

SIRS

Answer 1

Systemic Inflammatory Response Syndrome (need 2):
Temp: greater than 38 or less than 36 deg C
HR: greater than 90
RR: greater than 20
PaCO2: less than 32
WCC: less than 4,000 or greater than 12,000

+Infection = sepsis

+organ dysfunction or decreased perfusion/BP = sepsis/SIRS

+BP less than 90 or below 40 = sepsis/SIRS hypotension

+low perfusion/BP despite resuscitation = sepsis/SIRS shock

+ 2 or more organ dysfunction requiring intervention = Multi-organ dysfunction syndrome (MODS)

Question 2

What are the 3 main elements that drive a patient toward multi-organ dysfunction?

Answer 2

1. inflammation mediated by innate/adaptive immune system
2. endothelial injury
3. activation of blood clotting cascade

Question 3

Organ dysfunction variables

Answer 3

PaO2:FiO2 less than 300
Oliguria (less than 0.5 ml/kg/hr)
serum creatinine greater than 0.5 mg/dl
Coagulation abnormalities (INR above 1.5, or PTT greater than 60 s
Paralytic ileus
Thrombocytopenia (Platelets less than 100k/mm3)
Hyperbilirubinemia (total bili above 4 mg/dl)

Question 4

Hypoperfusion variables

Answer 4

hyperlactatemia (lactate above 1 mmol/liter)

Decreased cap refill or mottling

Question 5

Which is more problematic in sepsis, the bacteria or our body’s response to them?

Answer 5

Our response:
Primary sepsis mediators (IL1, TNF alpha, ROS, RNS, lipids)
Secondary mediators (NO, PAF, PG, LT, IL kinins)
Vicious cycle of hypoperfusion, ischemia, microcirculatory shunts, and acidosis. (Vasodilation, capillary leak, microvascular obstruction, myocardial depression)
MODS
Death

Question 6

Cell injury and inflammatory response

Answer 6

• Insult (infectious)
• Recognition (dendritic cells, tissue monocytes and macrophages)
• Secretion (pro-inflammatory cytokines)
• Neutrophils, mast cells, and inflammatory mediators activated/recruited to site
• Vasodilation, vascular permeability
• Fluid leak (vessels become low in volume. ie fluid is in the wrong place)
• Tissue factor is expressed
• Microcoagulation (Plasminogen, protein C, thrmbomodulin, antithrombin III and tissue factor pathway inhibitor production)
• Fibrinolysis is limited
• Microcoagulants occlude capillary blood flow and promote tissue ISCHEMIA. (Plug= inflamed cells, dying cells that release DNA, platelets, and neutrophil traps/NETS)
• Leads to relative hypovolemia and loss of vascular tone (eventually hypotension)

Question 7

How often in sepsis is an infectious organism found?

Answer 7

2/3: find organism (could be many things G+, G-, anaerobes, parasite, etc)
1/3: infectious organism is never found (so endogenous antigens may also trigger sepsis)

Non-bacterial infectious causes: influenza/H1N1 or viruses like Ebola, SARS

Question 8

Noninfectious mimics of sepsis

Answer 8

"7 As":
Acute MI
acute Pulmonary embolism
acute pancreatitis
acute GI bleeding
adverse drug reactions 
accidents: major trauma
(a)blaze: severe burns

Question 9

Most common sites of infection vs mortality

Answer 9

site:
respiratory
bacteremia
GU
abdominal

mortality:
bacteremia
respiratory
endocarditis
CNS

Question 10

Alterations in microcirculatory blood flow

Answer 10

• decrease in number of functional capillaries leads to inability to extract oxygen due to compression of capillaries and clogged capillary lumen
• so blood returns to right heart with a lot of oxygen (and tissue is ischemic)

Question 11

Mitochondrial dysoxia

Answer 11

-oxygen utilization by mitochondria is dysfunctional, but O2 delivery is preserved
(impaired pyruvate delivery, inhibition of Krebs cycle or ETC, failed maintenance of transmitochondrial membrane gradient with uncoupling of ATP synthase)
-leads to elevated serum lactate

=energy metabolism crisis in sepsis

Question 12

Late sepsis immune paresis

Answer 12

-low levels of B cells, T cells, and Dendritic cells in spleen in late sepsis due to prolonged hyper-inflammatory response (thus creating a hypoinflammatory response)

Question 13

Treatment of sepsis

Answer 13

“Bundled therapies”
-stabilize patient to allow time for things like antibiotics to take hold

1. routine sepsis screening
2. blood and respiratory cx
3. broad spectrum antibiotics
4. IV N/S 30ml/kg; add albumin
5. normalize serum lactate
   6 vasopressors
6. quantitative resuscitation targets (MAP above 65 mmHg, Urine output above 0.5 ml/kg/hr, etc)

Question 14

SOFA

Answer 14

Sepsis-related organ failure assessment score

• calculates number and severity of organ dysfunction in respiratory, coagulatory, liver, CV, renal, neurologic systems
• each organ given severity score 0-4

Question 15

Blood and respiratory cultures in sepsis dx

Answer 15

• gram stain provides limited info, can’t tell species or susceptibility
• culture too slow
• leads to ineffective and inappropriate therapy for some and therapy that is too broad for others

Question 16

When do you give antibiotics?

Answer 16

quickly, likely within first hour (the longer you wait, the more likely the pt is to die)

Question 17

Fluid therapy

Answer 17

-give large volume of fluids (around 2.5 L NS) to stabilize the patient