sepsis

Question 1

Sepsis

Answer 1

• Sepsis is a clinical syndrome that has phsyiologic, biologic, and biochemical abnormalities caused by dysregulated inflammatory response to infection.
• A life threatening organ dysfunction caused by dysregulated host response to infection.

Question 2

Pathophysiology of sepsis

Answer 2

• Sepsis results when the response to infection becomes generalized and involves normal tissue remote from the site of injury.
• Sepsis occurs when the release of proinflmmatory mediators in reponse to an infection exceeds the boundaries of the local environment, leadings to a more generalized response
  
  • When a similar process occurs in the response to a non-inflmmatory agent it is referred to as systemic inflammatory response syndrome

Question 3

Systemic effects of sepsis

Answer 3

• Widespread cellular injury may occur when the immune response becomes generalized - cellular injury is a precursor to organ dysfunction. Cellular injury is thought to be due to tissue ischemia (insufficient O₂ relative to O₂ needs), cytopathic injury (direct cell injury by proinflammaotry mediators and/or other products of inflammation) and an altered rate of apoptosis (in sepsis, proinflammatory cytokines and may delay apoptosis in acitvated macrophages and neutrophils - proloning the inflammaotry response and contributing to the development of multiple organ failure).

Question 4

Organ specific effects of sepsis

Answer 4

• Cellular injury along with release of proinflammtory and anti-inflammatory mediators often progresses to organ dysfunction. Although no organ system is protected from sepsism, some areas are more suspectible
• Circulation
  
  • Hypotension due to diffuse vasodilation. Likely due to release of vasoactive mediators.
  • Reduction in systolic and diastolic ventricular performance.
  • Redution in number of functional capillaries leading to an inability to use O₂ maximally.
• Lungs
  
  • Endothelial injury to pulmonary vasculature during sepsis distrubs capilaary blood flow and icnreases microvascular permeability, resulting in interstitial and alveolar pulmonary edema (results in V/Q mismatch and hypoxemia). Can manifest as ARDS
• GI tract
  
  • Circulatory abnormalities of typical sepsis may depress the gut’s normal barrier function allowing movement of the bacteria and endotoxin into the system circulation, extending the septic response.
• Kidney
  
  • Sepsis is often accompanied by AKI. One mechansim of this is acute tubular necrosis due to hypoperfusion and/or hypoxemia.
• Nervous system
  
  • CNS complications are frequent in septic patients. Most common CNS complications are encephalopathy.

Question 5

Disease severity sepsis

Answer 5

• Sepsis exists on a continuum of severity ranging from infection and bacteremia to sepsis and septic shock, that can ultimately leads to multiple organ dysfunction syndrome and death.
  *

Question 6

qSOFA

Answer 6

• Critieria for early sepsis. Score ≥ 2 is associated with poor outcome due to sepsis.
  
  • RR ≥ 22 - due to metabolic acidosis (lactate), hypoxemia, and fever (using convective mechanisms to try to cool down)
  • Altered mental status
  • Systolic blood pressure ( ≤ 100 mmHg)

Question 7

Septic shock

Answer 7

• A type of vasodilatory or distributive shock. Defined as sepsis that has circulatory cellular and metabolic abnormalities.
  
  • Includes patients who fulfill criteria for sepsis and who despite proper fluid resuscitatio require vasopressors to maintain a mean arterial pressure ≥ 65mmHg and have lacate > 2 mmol/L

Question 8

Clinical Presentation Septic Shock

Answer 8

• Symptoms and signs specific to an infectious source
• Arterial hypotension (SBP <90mmHg)
• Temperature > 38.3 or < 36
• Heart rate >90beats/min
• Tachypnea - RR >20
• Signs of end organ perfusion - warm, flushed skin in early phases; cool skin due to redirection of blood flow to core organs in shock; decreased cap refill, cyanosis, altered metnal status, oliguria, absent bowel sounds

Question 9

Management of Septic Shock

Answer 9

1. Securing airway, correcting hypoxemia, and establishing venous access for the early administration of fluids and antibiotics
2. Stabilize respiration - supplemental O₂ should be given. Intubation an mechanical ventilation may be requried.
3. Initial investigations:
   
   • CBC, liver function tests, coagulation studies
   • Serum lactate - elevated serum lactate may indicate the severity of sepsis
   • Arterial blood gas - may reveal acidosis, hypoxemia, or hypercapnia
   • Peripheral blood cultures (from at least 2 different sites), urinalysis, and microbiologic cultures
   • Imaging at suspected site of infection
4. Initial Resuscitative therapy
   
   • Rapid restoration of perfusion and early administration of antibiotics
     
     • Tissue perfusion is achieved by aggressive administration of IV fluids (either crystalloids or saline)
5. Vasopressors - IV vasopressors are used in patients who remain hypotensive despite adequate fluid resuscitation or who develop cardiogenic pulmonary edema.
   
   • Generally use norepinephrine as the first-line agent in septic shock
6. Patients who respond to therapy - once patients respond to therapy attention should be directed towards continuing to control the sepsis and de-escalation of fluids and antibiotics