Sepsis

Question 1

Pathophysiology of sepsis

Answer 1

• Bacteria or other pathogens are recognised by macrophages, lymphocytes and mast cells.
• These cells release cytokines like interleukins and TNF to alert the immune system of an invader
• Immune activation leads to release of further chemicals such as NO that causes vasodilation
• The full immune response causes inflammation
• Many of the cytokines cause the endothelial lining of blood vessels to become more permeable and so fluid can leak into the extracellular space causing oedema and reduced intravascular volume
• Oedema creates space between the vessels and the tissues reducing the amount of oxygen that reaches the tissues
• Activation of the coagulation system leads to deposition of fibrin throughout the circulation further compromising tissue and organ perfusion
• It also leads to consumption of platelets and clotting factors leading to thrombocytopenia, haemorrhages and DIC
• Blood lactate rises due to hypoperfusion of tissues leading to anaerobic respiration

Question 2

Definition of sepsis

Answer 2

• SIRS = ≥2 of:
  
  • Temperature >38^oC or <36^oC
  • RR >20
  • HR>90
  • WCC >12,000/mm³ or <4000/mm³
• Sepsis
  
  • SIRS
  • Source of infection
• Severe sepsis
  
  • Organ dysfunction, hypotension or hypoperfusion
• Septic shock
  
  • Severe sepsis with hypotension depsit adequate fluid resuscitation

Question 3

Severe sepsis

Answer 3

• Organ dysfunction includes:
  
  • Hypoxia
  • Oliguria
  • AKI
  • Thrombocytopenia
  • Coagulation dysfunction
  • Hypotension
  • Hyperlactaemia (>2mmol/L)

Question 4

Presentation of sepsis

Answer 4

• NEWS which involves:
  
  • Temperature
  • HR
  • RR
  • O2 saturations
  • BP
  • Consciousness level
• Other signs on examination
  
  • Signs of potential sources
  • Non-blanching rash can indicate meningococcal septicaemia
  • Reduced urine output
  • Mottled skin
  • Cyanosis
  • Arrhythmias such as new onset AF
• Key points:
  
  • High RR is often the first sign of sepsis
  • Elderly patients often present with confusion, drowsiness or simply ‘off legs’
  • Neutropenic or immunocompromiised patients may have normal observations despite being life threateningly unwell

Question 5

Sepsis 6

Answer 5

• O₂ to maintain sats (15l, trauma mask)
• Fluid (IV)
• Lactate
• Urine output
• Infection - blood cultures
• Drugs - empirical broad spectrum antibiotics

Question 6

Neutropenic sepsis

Answer 6

• Result of anti-cancer or immunosuppressant therapy
• Drugs include:
  
  • Anti-cancer chemotherapy
  • Clozapine (schizophrenia)
  • Hydroxychloroquine (RA)
  • Methotrexate (RA)
  • Sulfasalazine (RA)
  • Carbimazole (hyperthyroidism)
  • Quinine (malaria)
  • Infliximab (monoclonal antibody used for immunosuppression)
  • Rituximab (monoclonal antibody used for immunosuppression)
• Treated with antibiotics like tazocin (piperacillin with tazobactam)