Lecture 8 - Sepsis

Question 1

Sepsis

Answer 1

life threatening organ dysfunction caused by a dysregulated host response to infection

Question 2

Septic shock

Answer 2

sepsis with circulatory and cellular/metabolic abnormalities profound enough to substantially increase mortality (type of distributive shocks)

Question 3

SIRS criteria

Answer 3

must have >/= 2:

• Fever of more than 38C (100.4) or less than 36 (96.8)
• HR >90/min
• RR >20/min or PaCO2 <32mmHg
• WBC >12,000 or <4,000 or >10% bands

Question 4

What is the clinical criteria for sepsis -3, 2016?

Answer 4

sepsis: suspected or documented infection and an acute increase of >/= 2 sequential (sepsis related) organ failure assessment (SOFA) points (a proxy for organ dysfunction)
- at the bedside: use the quick SOFA (qSOFA)

Septic shock: sepsis and vasopressor therapy needed to elevated MAP >/= 65mmHg and lactate > 2mmol/L after adequate fluid resuscitation

Question 5

qSOFA

Answer 5

used at the bedside for sepsis

1 point each:
RR >22/min
AMS
Systolic BP <100mmHG

qSOFA >/= 2 identifies pts with suspected infection who are likely to have prolonged ICU stay or die in hospital

Question 6

What is the pathophysiology behind sepsis?

Answer 6

bacteria invades tissue
macrophages are triggered and release:
-proinflammatory mediators (TNF, IL 1, 2, 6)
-antiinflammatory mediators (inhibitors of above)

sepsis occurs when the release of proinflammatory mediators in response to infection in unbalanced and exceeds the boundaries of the local environment

“malignant intravascular inflammation”

Question 7

Endotoxin

Answer 7

cell wall component on Gram negative organisms
contributes to progression of local infection to sepsis
activates the complement, coagulation and fibrinolytic system

basically there are certain bacteria that are more likely to cause sepsis

Question 8

Which bacteria are more likely to cause sepsis?

Answer 8

Endotoxin (see in gram negative)

Gram Positive: 
Staph Enterotoxin B (staph aureus) 
TSS toxin -1 (staph aureus) 
Pseudomonas exotoxin
Group A strep M protein

Question 9

What signs qualify as end organ damage in sepsis?

Answer 9

hypotension from vasodilation, hypoperfusion of all organs

ARDS

encephalopathy

liver dysfunction/shock liver, elevated bili, clotting factors not made

acute renal failure, dec or absent urine output

systolic and diastolic ventricular dysfunction

DIC

Question 10

White out on CXR

Answer 10

ARDS

Question 11

ARDS

Answer 11

acute respiratory distress syndrome
predominantly a hypoxemic respiratory failure caused by alveolar edema
inability of the respiratory system to meet the oxygenation requirements

management: ventilate with low tidal volume (6mL/kg), control inflammatory response, prevent volume overload that can further congest lungs

Question 12

What is the management of ARDS?

Answer 12

ventilate with low tidal volume (6mL/kg), control inflammatory response, prevent volume overload that can further congest lungs

Question 13

DIC

Answer 13

Disseminated intravascular coagulation
“consumption coagulopathy”

coagulation and fibrinolysis become abnormally over-activated

• coagulation: formation of clot
• fibrinolysis: break down of clot
• overactive clotting stimulation depletes coagulation factors which causes further bleeding

risk of thrombosis and hemorrhage

Question 14

Acute vs chronic DIC

Answer 14

acute: more symptomatic with bleeding/thrombosis
chronic: often from cancer. less symptomatic; with evidence of DIC on labs

Question 15

What causes DIC?

Answer 15

stimulated by a procoagulant (tissue factor, bacterial lipopolysaccharides, procaogulant enzymes)

bacterial infection 
cancer
obstetrical complication 
trauma to tissues 
hemolysis from blood transfusion reaction

Question 16

How do pts with DIC present?

Answer 16

bleeding (sites of trauma, nose, drains, catheters)
thrombosis (DVT, PE, CVA, MI, microvascular)
thrombocytopenia
coagulopathy with long PT/INR, PTT
organ damage (kidneys, lungs, liver, brain)

clinical exa,: ecchymoses, petechiae, bleeding

Question 17

What labs do you expect to see for DIC?

Answer 17

PT/INR: elevated (extrinsic coagulation factors)
aPTT: elevated (intrinsic coagulation factors)
fibrinogen: low in DIC (might be high in the acute phase)
D-Dimer: elevated
Platelets: low (thrombocytopenia)
schistocytes

Question 18

How is DIC managed?

Answer 18

treat symptomatology:
if the pt is bleeding - treat by giving products (FFP, cryo)
if pt is clotting - give anticoagulation (heparin drip)
you basically have to sacrifice one for the other

replace lost blood volume with PRBCs

support pt: vasopressors, oxygen, ventilator

Question 19

How can you tell the difference between DIC and TTP?

Answer 19

TTP has a normal PT/INR and PTT because it does not involve coagulation factors

but you will still have (in both):
low fibrinogen, elevated d-dimer, thrombocytopenia, schistocytes

Question 20

What is the clinical presentation for sepsis?

Answer 20

ill-appearing 
fever
rigors 
AMS
tachycardia
tachypnea
hypotension 
elevated WBC, left shift/bandemia 
pain 

NOT EVERY SPETIC PT HAS A FEVER

Question 21

How do you manage septic shock?

Answer 21

stabilize respiration and establish venous access

identify source of infection

Labs: CBC, chemistry, LFTs, coags, lactate, ABG

give empiric antibiotics
admit to ICU
treat infection source
GET BLOOD CULTURE to narrow ABX therapy later

Question 22

What is an example of empiric antibiotic therapy for sepsis?

Answer 22

vancomycin + carbapenem +/- fluoroquinolone or aminoglycoside

Question 23

Hypovolemia

Answer 23

septic shock is associated with:
peripheral vasodilation
intra to extravascular fluid shifts

assess preload by exam and ancillary testing
bolus balanced crystaloid solution (LR, 0.9% NS) and reassess
watch for pulmonary edema, CHF
add pressors after euvolemic

Question 24

Hypotension

Answer 24

prolonged hypotension results in: tissue ischemia/anaerobic metabolism, inefficient ATP production and lactic acidosis

maintain MAP >/=65

select norepi as first line vasporessor

add “stress steroids” for shcok refractory to vasporessor therapy

Question 25

Lactate

Answer 25

sign of tissue hypoxia

lactate is a byproduct of anaerobic metabolism. cells go into anaerobic metabolism when there is not enough oxygen to complete aerobic metabolism

• lactic acidosis is a sign of hypoperfusion and hypooxygenation
• trending lactates can help determine severity of illness and prognosis. if pt is unable to clear lactate (down to a normal range of <2), this indicates poor prognosis

Question 26

What are the causes of septic shock?

Answer 26

PNA: most common
intra-abdominal infection
UTI
bacteremia: blood cultures are positive in 30-45% of septic pts

in up to 1/3 - 1/2 of cases, cultures from all sites are negative (“culture negative sepsis”)

Most common: gram negative
-e.coli, klebsiella, pseudomonas, enterobacter

gram +: staph aureus , strep pneumo

fungi: candida

Question 27

What are the components of SOFA?

Answer 27

respiration (PaO2) 
coagulation (platelets) 
liver (bili) 
cardio (MAP) 
GCS
Renal (Cr + urine output) 

to be considered sepsis (post 2016 criteria) a person must have 2+ of these + suspected infection

septic shock:
2+ SOFA + suspected infection + vasopressors needed to get MAP >/=65mmHg + lactate >2 mmol/L