Sepsis

 

• Background

  Life-threatening organ dysfunction caused by a dysregulated host response to infection.

  Pathophysiology

  • Pathogen recognition by immune cells – e.g. LPS-LBP endotoxin recognised by macrophages – leads to release of inflammatory mediators including TNFα, IL-1, and IL-6. This becomes generalised and eventually results in widespread cytokine activation.
  • Cytokines and inflammatory mediators lead to vasodilation, causing a distributive shock.
  • Microcirculatory failure and tissue hypoperfusion results from (a) inflammatory endothelial dysfunction and (b) an imbalance of coagulative and fibrinolytic mechanisms causing microvascular thrombosis, which may generalise to DIC.
  • Positive blood cultures support the diagnosis but are not required, and are only found in 1/3. Staph. aureus, Strep. pneumo, and Gram negative bacilli are the commonest pathogens.

  Definitions

  Sepsis-2 criteria

  Systemic inflammatory response syndrome (SIRS) is ≥2 of the following:

  • Temperature outside the range of 36-38°C.
  • WBC outside the range of 4-12.
  • HR >90
  • RR >20

  Sepsis syndromes:

  • Sepsis: SIRS + signs of infection.
  • Severe sepsis: sepsis + organ hypoperfusion and dysfunction.
  • Severe sepsis + SBP <90 after adequate fluid resuscitation.

  The limits of SIRS:

  • Only 1 in 4 patients with SIRS in the emergency department have an infection i.e. it has a low positive predictive value. Other causes of SIRS include trauma, burns, and pancreatitis, and any form of stress or exertion could cause the criteria to be met.
  • 1 in 8 patients with severe sepsis do not meet SIRS criteria (i.e. it has 88% sensitivity).

  Sepsis-3 criteria

  In 2016, new criteria were published, though their uptake has been variable.

  Screen for sepsis using qSOFA, where 2/3 should raise suspicion:

  • Altered mental status (GCS <15).
  • RR ≥22
  • SBP ≤100.

  Sepsis syndromes:

  • Sepsis: increase in SOFA (Sequential Organ Failure Assessement) score ≥2 points + signs of infection.
  • Septic shock: sepsis + vasopressors needed for MAP ≥65 mmHg + lactate >2 mmol/L.

  Multiple organ dysfunction syndrome (MODS)

  • Dysfunction of ≥2 organs.
  • Sepsis is the commonest cause.
  • Often includes encephalopathy, AKI, ARDS, and liver dysfunction. GI tract is also affected, and the associated epithelial dysfunction allows bacterial translocation and further propagation of the process.

• Signs and symptoms

  General signs include fever or ↓temperature, plus signs of distributive shock and organ hypoperfusion:

  • Abnormal obs: ↓BP, ↑HR, ↑RR.
  • Skin and peripheral changes: ↑cap refill, warm and sweaty and/or cold peripheries, mottled skin, petechial rash.
  • ↓Urine output.
  • Altered mental status (also reflects delirium).

  Local infection signs:

  • Pneumonia
  • Cellulitis
  • UTI
  • Meningitis
  • Peritonitis
  • However, there may be no obvious focal source.

• Management

  Initial investigations and treatment should ideally be completed within 1 hour, based on clinical suspicion and not requiring rigorous adherence to formal definitions.

  Investigations:

  • Cultures of blood and other fluids e.g. urine, CSF.
  • Bloods: lactate (key marker of severity), Hb, U&E (AKI), LFT (liver dysfunction, potential biliary source), coag (DIC), and glucose.
  • Measure and record fluid balance inc. urine output (consider urinary catheter).
  • Once initial tests done, imaging to look for source, guided by history and exam e.g. CXR, US abdomen, CT abdo-pelvis.

  Initial treatment:

  • IV antibiotics post-blood cultures. Broad spectrum – e.g. piperacillin/tazobactam – until blood culture results.
  • Fluids: start with 250-500 ml crystalloid challenge, and continue up to 30 ml/kg (≈ 2L for most), though some may need less or more.

  Further treatment:

  • Vasopressors for fluid-refractory shock: noradrenaline is typically 1st line, with vasopressin and adrenaline as further options.
  • Steroids (e.g. hydrocortisone) may be used in vasopressor-refractory shock, though evidence is mixed.
  • Source control e.g. surgery to remove gallbladder or drain abscess.

• Disseminated intravascular coagulation (DIC)

  Pathophysiology

  Pathway:

  • Initial trigger is a systemic inflammatory response, or a release of procoagulants (e.g. tissue factor) into the bloodstream from trauma or cancer.
  • Leads to widespread clotting, causing ischaemia and infarction.
  • Clotting factors eventually used up ('consumptive coagulopathy') leading to widespread bleeding, tissue hypoperfusion, and organ dysfunction.

  Causes:

  • Sepsis: commonest cause.
  • Cancer. Can also cause chronic DIC.
  • Major trauma.
  • Obstetric complications: placental abruption, amniotic fluid embolism, eclampsia.

  Signs and symptoms

  Acute DIC:

  • Signs of underlying pathology e.g. fever.
  • Widespread bruising and bleeding.
  • Liver and kidney dysfunction.
  • Respiratory dysfunction.
  • Confusion
  • Shock

  Chronic DIC:

  • Thrombosis

  Investigations

  • ↑PT and ↑APTT.
  • ↓Platelets and ↓fibrinogen.
  • ↑D-dimer

  Management

  Treat underlying cause and give blood products if actively bleeding:

  • Platelets if they are low.
  • Fresh frozen plasma (FFP) or prothrombin concentrate complex if ↑PT or ↑APTT.
  • Further option: cryoprecipitate.

• Acute respiratory distress syndrome (ARDS)

  Definition and pathophysiology

  • Bilateral pulmonary infiltrates (i.e. oedema) on CXR/CT plus hypoxaemia, not explained by heart failure.
  • Due to inflammatory injury to alveoli. Can progress to fibrosis.
  • Severity by PaO2/FiO2 ratio (mm Hg): mild ≤300, moderate ≤200, severe ≤100. This assumes PEEP of ≥5.
  • 30% mortality.

  Causes

  • Pneumonia and sepsis (inc. non-respiratory) are the commonest causes.
  • Trauma: lung contusions, burns, fat embolism.
  • Iatrogenic: massive transfusion, lung or bone marrow transplant, cardiopulmonary bypass.
  • Others: aspiration, acute pancreatitis, drugs.

  Management

  • Protective mechanical ventilation: low tidal volume and low airway pressure.
  • Avoid fluid overload.
  • Further options if severe: prone positioning, neuromuscular blockade, extra-corporeal membrane oxygenation (ECMO).