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.- 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
- 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
- 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
- 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
- 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
- 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).
Baby check at birth and 6 weeks Check notes and get equipment ready: Measuring tape. Ophthalmoscope Sats probe. In notes, look at full details of pregnancy and birth, including Apgar scores at 1 and 5 minutes. Observation: Colour: pink/red, pale, jaundiced. Any rash? Erythema toxicum is a self-limiting rash of red papules and vesicles, surrounded by red blotches which sometimes give a halo appearance. Usually occurs between 2 days and 2 weeks. Behaviour and mood. Movements. Face: dysmorphism? Head: Feel fontanelle (bulging? sunken?) and sutures. Note that posterior fontanelle closes at 1-2 months, and anterior at 7-19 months. Measure circumference at widest point; take the highest of 3 measurements. Looking for hydrocephalus and microcephaly. Eyes: check red reflex with ophthalmoscope. Feel inside top of mouth with little finger for cleft palate. Also gives you the sucking reflex. Inspect ears to see if they are low-set (below eye level), have any tags or lumps, and check behind the
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