Meningococcal sepsis

Meningococcal sepsis keeps showing up in ICU and in ICU exams, which makes it a sensible revision topic for the end-stage trainee.

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• N.meningitides  featured in  Question 10 from the second paper of 2002: "Outline the diagnostic features, complications and treatment of patients  with meningococcal sepsis."
• It also appeared in the ABG interpretation scenario for Question 3.1 from the second paper of 2015, where the trainees were expected to identify the meningococcaemia on the basis of "fever, headache and a widespread rash". The patient also had a horrific blood gas with features of hypoadrenalism, consistent with Waterhouse-Friedrichsen syndrome.
• It was again the central topic of Question 22 from the second paper of 2023, where risk factors clinical features and management were asked about.

A good NEJM review article is available which covers this territory well. It is the source for most of the information offered in the summary below. If one wished to cultivate an intimate acquaintance with N.meningitides, one may consider reading Rouphael and Stephens' massive opus from 2012.

The microorganism

• Gram-negative aerobic diplococcus 
• An encapsulated organism, resistant to opsonization- its capsule protects it against complement-mediated bacteriolysis and phagocytosis by neutrophils, Kupffer cells, and spleen macrophages.
• A fastidious bacterium: it dies within hours on extracorporeal surfaces.
• A well-adapted human pathogen: its transferrin-binding proteins steal iron from the human host.
• It readily invades the meninges, and many patients with menigococcal sepsis will also have meningitis.
• It is virtually defenceless against antibiotics.  Antibiotic resistance to anything except for sulfonamides is very rarely seen. Usually, straightforward benzylpenicillin is enough.

Defence against N.meningitides:

• Antibody-mediated immunity is the most potent defence
• The peak incidence of the disease occurs in the first year of life
  (following the loss of maternal antibody)
• Progressively less common throughout childhood
• Extremely rare in immunocompetent adults
• Becomes more common in the post-splenectomy state

Clinical features of meningococcal sepsis

• Abrupt onset of high fever
• Myalgias, arthralgias, headache, decreased level of consciousness
• Petechial or purpuric rash
  • Digital ischaemia
  • progression to purpura fulminans (this is one of the differentials for purpura fulminans)
• Hypotension and shock
• Characteristic severe myocardial depression
• Blood or CSF cultures positive for N.meningitidis
• PCR of peripheral blood (apparently, it is useful for diagnosis of meningococcal disease)

Risk factors for meningococcal sepsis

From the CDC, 

• Immune compromise (eg. splenectomy, chemotherapy, complement deficiency, HIV)
• Close contact with nasopharyngeal secretions from a case 
• Crowded living conditions, eg. institutionalisation or incarceration
• Smoking
• Young age (under 12 months) or old age (over 65)
• Travel to the "meningitis belt" in sub-Saharan Africa 

Complications of meningococcal sepsis

Acutely, it'd have to be:

• Septic shock
• DIC
• Acute adrenal haemorrhage (Waterhouse-Friedrichsen syndrome)
• Multiorgan system failure
• Meningitis
• Conjunctivitis
• Arthritis
• Pericarditis

But in the long term, patient-meaningful complications would include:

• Physical
  • Amputations (8% of children, 3% adolescents/adults)
  • Skin scars  (55% of children, 18% adolescents, 2% adults)
  • Chronic renal failure
  • Adrenal insufficiency
• Neurological
  • Hearing loss (8%) or tinnitus
  • Blindness
  • Cranial nerve palsies
  • Persistent cognitive dysfunction
• Psychological
  • Anxiety, PTSD
  • Learning difficulties
  • Emotional and behavioural difficulties

These are from the abstract of this excellent systematic review which contains a whole table for long term sequelae, which is too large to include here but which has merit as a reference. The percentage values are for adults (in children and infants the complication rates are higher).

Management of meningococcal sepsis

Antibiotics:

• Most strains are susceptible to penicillin.
• The Sanford Guide recomends ceftriaxone 2g bd or benzylpenicillin 2.4g q4h
• Chloramophenicol is an alternative, but apparently there has gradualyl been a worldwide development of resistance (and, worldwide there has been a gradual resistance developing to the use of chloramphenicol, as it is a dangerous drug perhaps better suited as a chemotherapy agent for haematological malignancy).
• Supportive management consists of vasopressor support and fluid resuscitiation, with correction of DIC-associated coagulopathy
• Corticosteroids may be useful if meningitis is present, but in the absence of meningitis they are not indicated except as management of relative adrenal insufficiency.
• Plasma exchange may improve survival if commenced early, but the evidence for it is not robust.