What is sepsis?
The systemic response to infection
What is SIRS defined as?
The presence of at least 2 of the following criteria, one of which must be abnormal temperature or leukocyte count;
- Temperature abnormalities
- Respiratory rate abnormalities
- Heart rate abnormalities
- White cell count abnormalities
What is tachycardia defined as in the definition of SIRS?
Mean heart rate >2SD above normal for age in the absence of external stimulus, chronic drugs or painful stimuli, or otherwise unexplained elevation over a 0.5-4 hour time period
What is classified as a heart rate abnormality in SIRS?
Tachycardia, or in children <1 year old bradycardia
What is bradycardia defined as in the definition of SIRS?
Mean heart rate <10th percentile for age in the absence of external vagal stimulus, beta-blocker drugs, or congenital heart disease, or otherwise unexplained persistent depression over a 0.5hour time period
What is classified as a respiratory rate abnormality in SIRS?
Raised respiratory rate, or mechanical ventilation for an acute process not related to underlying neuromuscular disease or general anaesthesia
What is raised respiratory rate defined as in the definition of SIRS?
Mean respiratory rate >2SD above normal for age
What is classified as white blood cell abnormalities in SIRS?
Leukocyte elevated or depressed for age (not secondary to chemotherapy-induced leukopenia) or >10% immature neutrophils
Give 4 causes of SIRS
- Infection
- Trauma
- Burns
- Pancreatitis
What is infection defined as?
Suspected or proven infection caused by any pathogen, or clinical syndrome associated with high probability of infection
How can an infection be proven?
Positive culture, tissue stain, or PCR test
Give 5 examples of evidence of infection
- Positive findings on clinical exam
- White blood cels in normally sterile body fluid
- Perforated viscus
- Chest radiograph consistent with pneumonia
- Petechial or purpuric rash, or purport fulminans
What is sepsis defined as?
SIRS in the presence of or as a result of suspected or proven infection
What is severe sepsis defined as?
Sepsis plus one of;
- Cardiovascular organ dysfunction
- Acute respiratory distress syndrome
- Two or more other organ dysfunctions
What is the characteristic pattern of severe sepsis?
Worsening cardiovascular, respiratory, and subsequently other organ system dysfunction
What is septic shock defined as?
Sepsis and cardiovascular dysfunction
What is classified as a temperature abnormality in SIRS?
Core temperature >38.5 or <36
What has led to a change in the causative agents of septicaemia in children?
Introduction of conjugate vaccinations
What pathogens causing septicaemia has there been a major reduction in since the introduction in vaccines?
- N. meningitidis
- Vaccine serotypes of S pneumonia
- Hib
What pathogens have increased in incidence since vaccine introduction?
- Non vaccine serotypes of S. pneumonia
- E. coli
- S. aureus
- Group A streptococcus
What is toxic shock syndrome?
An acute febrile illness caused by S. aureus or Group A streptococcus
What is toxic shock syndrome characterised by?
- Hypotension
- Multi-organ function
What causes hypotension and multi-organ dyfunction in toxic shock syndrome?
Bacterial exotoxins that act as superantigens
By how much has the hospital mortality of meningococcal sepsis fallen?
From over 90% in the mid 20th century to around 10% currently
What has caused the reduction in hospital mortality of meningococcal sepsis?
- Improvements in public awareness
- Early recognition and management
What is most of the pathophysiology of sepsis caused by?
Activation of host immune mechanisms triggered by numerous bacterial factors
How long can the activation of host immune mechanisms continue for after eradication of causative micro-organisms by appropriate antibacterial therapy in sepsis?
For days or weeks
How do bacterial factors activate the immune system in sepsis?
Bacterial cell wall components bind to and stimulate inflammatory and vascular endothelial cells via a variety of mechanisms
What happens when monocytes are stimulated in sepsis?
They produce a range of pro-inflammatory cytokines, including tumour necrosis factor alpha
What are cytokine levels closely correlated with in sepsis?
Disease severity and risk of death
What happens when neutrophils are stimulated in sepsis?
They undergo a respiratory burst with the production of reactive oxygen species, as well as degranulation and the release of a range of inflammatory proteins, proteases, and other enzymes.
They also contribute to the damage seen at the endothelial surface
What is the main pathophysiological event occurring in bacterial septicaemia?
The change in the vascular endothelial surface
What is the normal function of the vascular endothelial surface?
- Regulates vascular permeability
- Presents a thromboresistant, non-reactive surface to circulating blood cells
What happens to the normal functions of the vascular endothelial surface in sepsis?
They are lost
What processes affecting the microvasculature occur in sepsis?
- Increased vascular permeability
- Pathological vasoconstriction and vasodilation
- Loss of thromboresistance and intravascular coagulation
- Myocardial dysfunction
What is the consequence of increased vascular permeability in sepsis?
- Hypovolaemia
- Oedema in organ and tissues
How is hypovolaemia initially compensated for in sepsis?
Homeostatic mechanisms, including vasoconstriction of both arterial and venous vascular beds
What happens as capillary leak progresses past what can be compensated for with homeostatic in mechanisms in sepsis?
Venous return to the heart is impaired and cardiac output falls
What is the most important component of resuscitation in hypovolaemia caused by sepsis?
Restoration of circulating volume
What is the problem with restoring circulating volume in hypovolaemia caused by sepsis?
It can increase the risk of increasing oedema in all tissues and organs as a result of persistent capillary leak
Where might fluid accumulate due to increased vascular permeability in sepsis?
- Tissue and muscle compartments
- Peritoneal space
- Pleural space
- In alveoli
What acts as an early protective measure in sepsis?
Compensatory vasoconstriction
What is the purpose of compensatory vasoconstriction in sepsis?
To maintain tissue and organ perfusion in the face of diminished cardiac output
Does vasoconstriction always improve following resuscitation in sepsis?
No, it may persist
What is cold shock?
When patients with severe vasoconstriction develop cold, pale, and ischaemic limbs
What is warm shock?
When patients develop profound vasodilatation following resuscitation, with bounding pulses, warm peripheries, and hypotension
Who usually develops warm shock?
Older children
What management does warm shock usually respond to?
Fluid resuscitation and vasopressors such as noradrenaline
What is the hallmark of severe meningococcal sepsis?
Widespread purpura fulminans with thrombosis and haemorrhagic necrosis in the skin
What can haemorrhagic necrosis cause in extreme cases of severe meningococcal sepsis?
Infarction and gangrene of limbs and digits
What causes the purpura, thrombosis, and haemorrhagic necrosis in severe meningococcal sepsis?
Disruption of the normal anti-thrombotic properties of the vascular endothelial surface and impairment of natural anticoagulant pathways and fibrinolysis
What abnormalities are found on blood tests due to disruption of normal coagulation pathways in severe meningococcal sepsis?
- Profound thrombocytopenia
- Prolonged coagulation
Why do you get profound thrombocytopenia and prolonged coagulation in severe meningococcal meningitis?
As platelets and clotting factors are consumed as clot is formed in small vessels
What further increases the likelihood of thrombosis in the skin and peripheries in severe meningococcal sepsis?
Sluggish capillary circulation and intense vasoconstriction
What causes the low cardiac output seen in sepsis?
- Hypovolaemia
- Decrease in myocardial contractility
What causes the hypovolaemia leading to low cardiac output in sepsis?
- Capillary leak
- Loss of circulating volume
Does the decrease in myocardial contractility seen in sepsis persist after correction of circulating volume?
Yes
What causes the development of myocardial dysfunction in meningococcal sepsis?
The negative inotropic effect of pro-inflammatory mediators, especially IL-6
What factors common to all types of sepsis can adversely affect myocardial function?
- Hypoxia
- Acidosis
- Hypoglycaemia
- Hypokalaemia
- Hypocalcaemia
- Hypophosphataemia
What may be required to manage the myocardial dysfunction in sepsis?
Very high doses of inotropes
What is the long term impact of myocardial dysfunction in sepsis?
Most patients recover without any long-term consequences
