Sepsis

Question 1

Sepsis definition

Answer 1

• SIRS + infection
  
  • Temp >38C or <36C
  • HR > 90
  • RR > 20
  • PaCO₂ <32

Question 2

Sepsis/SIRS Septic shock

Answer 2

1. SIRS = Temp: >38,<36 HR: >90 RR: >20, PaCO2<32
2. • infection
3. • organ dysfxn OR decreased perfusion/BP
     1. BP < 90 (or decreased by 40 from baseline)
4. • decreased perfusion/BP despite resuscitation

Question 3

Multiple organ dysfxn syndrome definition/criteria

Answer 3

1. SIRS = Temp: >38,<36 HR: >90 RR: >20, PaCO2<32
2. • infection ==> sepsis
3. • organ dysfxn OR decreased perfusion/BP
4. BP < 90 (or decreased by 40 from baseline)
5. • decreased perfusion/BP despite resuscitation ==> septic shock
6. • >=2 organ dysfxns requiring intervention ==> MODS

Question 4

Organ dysfxn variables

Answer 4

• Pulmonary = PaO2 : FiO2 <300
• Renal
  
  • • Oliguria (UOP <0.5 ml/kg/hr)
  • • Se creatinine ↑>0.5 mg/dl
• Hemat
  
  • • Coagulation abnormalities (INR >1.5; or aPTT >60 sec)
  • • Thrombocytopenia (Platelets <100k/mm3)
• GI
  
  • • Paralytic ileus
• • Hyperbilirubinemia

Question 5

Common causes/infections ==> sepsis

Answer 5

1. Respiratory
2. Genitourinary
3. Wound/soft tissue
4. abdominal

Question 6

Types of organisms that causes sepsis

Answer 6

1. gram-negative bacteria positive (60%)
2. gram-positive bacertia positive (45%)

Question 7

Highest mortality infection sites ==> sepsis

Answer 7

1. Endocarditis
2. Respiratory
3. CNS

Question 8

Risks for developing sepsis

Answer 8

• male sex
• race: non-caucasian > caucasians
• age (older)
• comorbid medical conditions
  
  • between 6 and 30% of all intensive care unit (ICU) patients
• alcohol abuse
• lower socioeconomic status
  *

Question 9

Early cellular and molecular events during infection

Answer 9

1. vasodilation and endothelial activation
2. leukocyte recruitment and activation
3. coagulation and NET formation

Question 10

General path ==> sepsis

Answer 10

1. local growth of pathogen w/low load of bacteria and inflammation
   
   1. effective immune response ==> contained infection, bacterial clearance, limited immune system activation, no organ fail
2. innefective immune response ==> systemic bacterial dissemination
   
   1. systemically elevated cytokines
   2. multiple organ failure

Question 11

Energy metabolism crisis in sepsis

Answer 11

• Mitochondrial “dysoxia” or Cytopathic Hypoxia: Oxygen utilization (VO2) by the mitochondria is dysfunctional, but oxygen delivery (DO2) is preserved!
• • Impaired pyruvate delivery
• • Inhibition of Krebs cycle or electron transport chain
• • Activation of poly(ADPribosyl) polymerase (PARP)
• • Failed maintenance of the transmitochondrial membrane gradient with uncoupling of ATP synthase.

Question 12

Characteristics of immune fxn in early and late sepsis (+consequences)

Answer 12

• Early sepsis
  
  • T_H1 cytokines and chemokines ==> hyperinflammatory response
  • ==> death w/acute organ dysfxn due to cytokine storm
• Late sepsis
  
  • Apoptotis depletion of immune cells + T_H2 responses ==> hypoinflammatory response
  • ==> death due to primary infection or development of secondary infection

Question 13

(General) characteristics of surviving sepsis caampaign

Answer 13

• RESUSCITATION BUNDLE
• Start immediately complete within 3 hours
• “Surviving Sepsis v2014”
• Multimodal treatment for Severe HCAP, Septic Shock/MODS

Question 14

Steps in the surviving sepsis resuscitation bundle

Answer 14

• 1. Routine Sepsis Screening (1C)
• 2. Blood & Respiratory Cx
• 3. Broad Spectrum Abx-1 hr
• 4. IV N/S 30mL/kg in 1st 2 hr
     * • Add albumin (2B)
• 5. Normalize Serum Lactate (2C)
• 6. Vasopressors:
     * • Norepinephrine 10μg/min (1B)
     * • Epinephrine added or alternative (1C)
     * • DOPA only in selected (2C)
     
     • • ?Vasopressin:
     • • Dobutamine:
• 7. Quantitative Resuscitation Targets (Shock, Lactate>4)
     * • MAP≥65 mm Hg
     * UOP ≥ 0.5 mL/kg/hr

Question 15

Sepsis Recognition: TAKE HOME POINTS!

Answer 15

• • Severe sepsis is a very common, life-threatening complication in hospitalized patients
• • The diagnosis may be subtle
• • Evaluate for trends over time (i.e. VS, UO, CNS)
• • For prompt recognition, consider severe sepsis as the cause of any new unexplained symptoms, signs, or laboratory abnormalities, even when you don’t suspect infection
• • Always assess the severity of sepsis
• • Even when illness seems mild, by VS/appearance, ALWAYS √ lactate and screen for organ dysfunction

Question 16

Why do novel therapies for sepsis (nearly all) fail in clinical trial?

Answer 16

• • Inadequate phenotyping, prevention and delivery of care
  
  • • No reliable biomarkers for risk & disease progression
  • • No personalized approaches to risk stratification
  • • Suboptimal standardization for 1^oresusc.
• Inadequate molecular mechanistic understanding
  
  • • Activated protein C: ePCR vs anticoagulant properties
  • • Antibody blockade of single cytokines unsuccessful: TNF and IL-1β
• • Ineffective therapeutic targeting:
  
  • • Late mediators - vascular leak and end organ damage
  • • Enhancing anti-inflammatory, anti-bacterial, and repair pathways •
  • Mitigating post-septic immunosuppression by immunostimulation