Acute Inflammation

  • Non-specific response to injury due to a number of different tissue insults which can be endogenous or exogenous e.g. infection, ishaemia (hypoxia), trauma, toxin exposure
    • Aim is the rid the cause and consequences of injury; however, inflammation can be harmful
  • Lasts minutes-days (longer than this is chronic inflammation)


  • Mediated by mostly chemical mediators e.g. bacterial toxins, histamine, serotonin, arachidonic acid, metabolites, cytokines, complement factors etc
    • The clotting system and inflammation are connected (bleeding causes inflammation)
    • The predominant cell type in acute inflammation is the neutrophil (macrophage is a cell of chronic inflammation).
  • Phases
    1. Widespread vasodilation (hyperaemia)
      1. Initially, if there is vascular injury, there is a rapid and transient vasoconstrictor response to avoid excess blood loss and to allow clot formation
      2. Platelet activation causes the release of various chemical mediators including prostaglandins, leukotrienes, histamine and serotonin
      3. Prostaglandins and nitrous oxide released cause widespread vasodilation, whilst serotonin, histamine and serotonin cause increased permeability
      4. They also cause recruitment of other cells involved, as well as activation of the complement cascade.
    2. Increased vascular permeability
      1. Immediate-transient response (occurs in every case)- only affects venules, in response to inflammatory mediators released in response to the insult.  Caused by contraction of the endothelial cells (causing larger intercellular gaps)
      2. Immediate-prolonged response- similar to transient but occurs when the stimulus is prolonged, causing a prolonged ‘immediate’ response.
      3. Delayed prolonged leakage- seen after hours or days.  Usually due to apoptosis of endothelial cells which opens up intercellular space to cause protein/fluid leak.  A good example is that of sunburn (delayed inflammation)
    3. Leucocyte extravasation and phagocytosis
      1. Margination- as blood flow decreases, leucocytes move from the centre to the edge of the vessel
      2. Rolling and adhesion (pavementing)- activated endothelial cells express intercellular adhesion molecules (e.g. ICAM-1), which bind to adhesion molecules on the leucocytes (integrins)
        1. Note ICAMs are upregulated in many inflammatory diseases and down-regulated in conditions such as diabetes, alcohol excess, steroid excess.
      3. Diapedesis or Emigration across the endothelium
      4. Chemotaxis/migration- attracted by complement factors and leukotrienes, amongst others (e.g. TGF; VEGF etc)
  • Note that neutrophils are the primary inflammatory cell recruited in the first 24 hours.  Macrophages become predominant after 48 hours.

Inflammatory mediators

  • See also complement
  • Kinin system
    • Activation of coagulation factor XII into factor XIIa sets off a series of enzyme reactions which results in the production of bradykinin.
    • Bradykinin is a potent vasodilator and increases vascular permeability.
  • Histamine and serotonin (mast cell/basophils and, to a smaller degree, platelets)
    • Release stimulated by C3a/C5a, bound IgE and IL1
    • Both are also potent vasodilators and increase vascular permeability.
  • Nitric Oxide (NO)
    • Produced by NO synthase by neurons, endothelial cells and the immune system
    • Acts to reduce intracellular calcium which causes smooth muscle dilatation, decreased cardiac contractility, reduced platelet and inflammatory cell activation
      • This can be protective in neurons and endothelial cells but can be pathological in acute inflammation (local vasodilator; bactericidal; downregulates neutrophil function but prolongs their lifespan; conversely induces apoptosis in macrophages)
  • Arachidonic Acid Derivatives
    • Arachidonic acid is present in cell membranes and is activated in acute inflammation by phospholipases which release it from the membrane.
    • It is then metabolised by one of two pathways
      • COX pathway to produce prostaglandins
        • These cause vasodilation, increased vascular permeability and can be hyperalgesic
      • Lipoxygenase pathway to produce Leukotrienes 
        • Cause increased permeability; constrict smooth muscle cells and act as a chemotactic agent to attract inflammatory cells
  • Other mediators include polypeptides, interferons (involved in protection against viral infection), interleukins (powerful chemotactic and proliferation agents), TNF-α, and free radicals (powerful enzymes used to break down invading/foreign cells)


  • Redness (rubor)
  • Swelling (tumor)
  • Heat (calor)
  • Pain (dolor)
  • Also loss of function and increased secretion

Complement system


  • A response of the innate immune system
    • A series of >20 proteins that circulate in the blood, usually inactive but in response to inflammation or immune response, activate in an enzyme cascade which promotes chemotaxis of inflammatory cells, triggers the lytic pathway to break down foreign bodies, causes opsonisation of foreign cells, as well as cause the release/activation of further inflammatory mediators


  • There are several ways in which the complement system can be activated
  • Classical Pathway
    • Activated by immobilised antigens (antigen-antibody complexes- most effectively by IgM complexes) i.e. antibody dependent
    • Binds to C1q component of the complement system.  This then activates C1r and C1s.
      • This cleaves C4 and then C2 into C4b and C2a (respectively), which form a new enzyme C3 convertase.
      • This cleaves C3 into C3a and C3b.  C3 convertase combines with C3b to form C5 convertase (or C4b2a3b).
      • This cleaves C5 into C5a and C5b.  C5b is the first protein of the membrane attack complex.
  • Lectin Pathway
    • Identical to classical pathway except begins with mannose binding protein instead of C1.
    • Mannose binding protein binds to carbohydrates on the cell surface of foreign cells.  Once bound, it can cleave C4 and C2.
  • Alternative Pathway
    • 2 mechanisms for alternative pathway activation: Non-self cell absent and non-self cell present
    • Non-self cell absent (fluid phase activation)
      • Occurs continuously, spontaneously and slowly.
      • C3 spontaneous activates by hydrolysis into C3(H20).  This is unstable and usually reverts back to C3.  But on encounter with Factor B, interaction occurs to form C3(H2O)B.
        • This can be cleaved by Factor D into C3(H20)Bb- or fluid phase C3 convertase.  This cleaves C3 and the pathway is completed as in the classical pathway.
    • Non-self cell present
      • Much faster.
      • C3 binds to the non-self cell, which then interacts with Factor B … etc
      • C3 often smothers the cell surface, targeting it for macrocytosis by macrophages and granulocytes with C3b receptors.

Membrane Attack Complex

  • C5b binds to C6, C7 and C8, as well as several molecules of C9 to form MAC
  • It forms a pore in the lipid bilayer of foreign cell, causing water to rush in the cell and burst (cell lysis).

Other functions of the complement system

  • Cell lysis is only effective against cells without cell walls e.g. Gram-negative organisms.  It is not active against cells with cell walls (gram-positive organisms/fungi)
  • Other functions include
    • Opsonisation
      • Preparation of cells for phagocytosis (primarily via binding of C3b- which can interact with macrophages and polymorphic neutrophils
    • Inflammation
      • C3a, C4a and C5a are also anaphylotoxins and cause inflammation by binding to mast cells as well as inducing the production of pro-inflammatory cytokines.
      • C5a is also involved in chemotaxis, or attraction of lymphocytes/macrophages to the site of inflammation.
    • Immune clearance
      • C3b also binds to red blood cells and facilitates removal of non-self cells from the blood stream as it passes through the spleen and liver

Principles of Sedation


  • Used to alleviate distress/discomfort during procedures.
    • e.g. Premedication anxiolytic
    • As an amnesiac (e.g. with joint relocations/tooth removal)
    • As an adjunct to regional anaesthesia for larger procedures
    • For invasive procedures e.g. endoscopy
    • In critical care- to tolerate ET tube
  • Can be used to avoid general anaesthetic.  It has the advantage of a quick recovery and also does not require manipulation of the airway/ventilation as this is usually maintained by the patient.


  • Minimal Sedation
    • Drug induced state in which the patient response normally to verbal commands, and airway reflexes, ventilatory function and cardiac function are maintained.  Cognitive function and physical coordination may be impaired.
  • Moderate Sedation
    • A purposeful response to verbal commands either alone or with light tactile stimulation is maintained (i.e. conscious sedation– where verbal contact can be maintained).  The airway and ventilatory function is usually unimpaired.
  • Deep Sedation
    • Cannot be easily aroused but does respond purposefully to repeated or painful stimulation.  Respiratory effort may be depressed and the patient may require assistance in maintaining their airway (+/- positive pressure ventilation).

How to…

  • Pre-assessment
    • As well as modifying the sedation drug/dose based on patient weight, comorbidity, age etc (whilst this is important, most sedation involves a start low/go slow/titrate to effect approach to avoid immediate overdose)…
      • It is more important to ask “will I be able to resuscitate/ventilate this patient if they become over-sedated?”
    • Note fasting is only indicated for deep sedation/moderate sedation
  • Sedate
    • Minimal Sedation
      • This can usually be achieved by using opioids (Fentanyl is good if IV route available as it is rapid acting and has a fairly short half life- start with 25 microgram bolus- titrate to effect) and benzodiazepines (midazolam is good if IV route available- for the same reasons- start with 0.5-1mg and titrate to effect)
        • Note frail/elderly patients may be accutely susceptible to the effect of midazolam (may cause deep sedation at low doses) and opiates.
        • If using the oral route, 0.5mg lorazepam +/- 5-10mg of oramorph taken 30 mins or so prior to the procedure may be adequate (only really for minor procedures for anxiety more than anything)
      • Nitrous oxide may also be used for minimal sedation.
    • Moderate/conscious sedation
      • Ketamine is often used (analgesic at 0.1mg/kg; sedation at 0.5-1mg/kg- start with this and titrate to effect)
        • can cause increased secretions
    • Deep sedation
      • Usually anaesthetic agents such as propofol (0.5mg/kg initially and titrate to effect) or high doses of benzodiazepines
    • Titrate to effect is key to good sedation.
  • Monitor
      • Including ECG/cardiac monitoring, SpO2 saturations (all patients should have some form of oxygen supplementation)
      • Regularly neurological assessment/responsiveness should be checked to avoid over/under-sedation
        • NOTE THAT UNDERSEDATION CAN BE AS SIGNIFICANT AS OVER-SEDATION (undersedation may warrant a higher dose of drugs or even progression to GA if not working- it is essentially a pointless exercise if the patient is undersedated).

Side effects

  • Laryngospasm/stridor (< 0.3% rare). It usually subsides as the patient wakes. Can be managed with bag-valve mask with PEEP valve if patient apnoeic- may require GA/ventilation if it does not respond. If occurring post procedure with spontaneously ventilating patient treat with adrenaline nebs (5ml of 1:1000)
  • Apnoea – expect 15-30 s apnoea in around 1:20 patients in level 3 sedation. This is treated by manipulation of a misaligned airway first and followed if necessary by a gentle BMV. It should be detected early by monitoring ET CO2
  • Hypoxia from respiratory depression (SpO2<90mmHg). Provide high flow O2
  • Transient hypotension – SBP <100mmHg; this is common and if persistent should be treated with fluid boli 250-500ml
  • Bradycardia (HR<50bpm). Be prepared to monitor and treat with Atropine 500mcg if compromising patient
  • Level of sedation. The relief of pain consequent upon a successful procedure often means the patient will be increasingly sensitive to sedative agents. If the patient wakes to voice or tactile stimulus then no action is required other wise consider the use of reversing agents as appropriate
  • Specific drug side effects (Especially ketamine)

Regional Anaesthesia

  • Field Block- blocks the entire surgical field by infiltrating the nerve(s) supplying that region
    • Ring Block- a subtype of field block, usually applied to a digit or the penis, whereby everything distal to the block is anaesthetised.  (Note that adrenaline should NOT be used for ring block as it risks causing critical ischaemia to the affected area).

There are several regions which can be anaesthetised in this way.  For a more comprehensive list with where to inject, see the FRCA website here

  • Brachial Plexus (upper limb/shoulder)
    • Interscalene block
      • Targets the trunks of the brachial plexus, achieving anaesthesia best in C4-7
      • Useful for shoulder surgery/relocation
    • Supraclavicular block
      • Targets the divisions of the brachial plexus, achieving anaesthesia best in C5-T1
      • Useful in arm surgery
    • Axillary block
      • Targets the cords of the brachial plexus, achieving anaesthetic best in C7-T1 (musculocutaneous nerve)
      • Useful in distal arm/hand surgery
  • Femoral Nerve block
    • Anatomy
      • Arises from L2-4; runs deep to psoas in the groove between it and the iliacus muscle.  Lies on the iliopsoas as it passes under the inguinal ligament, lateral to the femoral artery (1cm at this point; 2cm at 1-2cm below the inguinal ligament).
    • Effect
      • Femoral nerve only (anterior thigh, knee and femur) OR ‘3 in 1’ block if using more anaesthetic and apply pressure distal to injection site (effects obturator and lateral cutaneous nerves too- i.e. most of the thigh)
  • Sciatic Block
    • Arises from L4-S3 and exits under the biceps femoris muscle.  It then splits into the common peroneal and tibial nerves which run down the centre of the thigh.
    • There are several approaches to infiltrating the sciatic nerve (see FRCA)- although it can be found 2cm lateral to the ischial tuberosity at the level of the greater trochanter.
    • Useful for lower limb (ankle/foot) surgery; may be combined with femoral block for whole leg surgery
  • Bier’s Block
    • This is IV regional anaesthesia, commonly used in the upper limb for distal fracture relocations/surgery
    • Method
      • Elevate the arm and then inflate a double cuff tourniquet over the upper arm to 300mmHg or 100mmHg above SBP (whichever is greater), effectively exsanguinating the arm.
        • There should be no radial pulse
      • Inject the anaesthetic (usually prilocaine) IV
      • To prevent pain, it may be suitable to inflate the lower cuff over the affected area after anaesthetisation, then release the upper cuff.
    • This requires close monitoring (of the cuff, the limb, and the patient) and the procedure should not last more than 45 minutes to prevent critical ischaemia
    • It is most commonly used for the relocation of Colles’ fractures.
  • Intercostal nerve blocks
    • Can effectively choose any intercostal nerve.  Useful for anaesthetising one area for procedures e.g. chest drain insertion; or for pain relief e.g. flail chest/rib fracture.
    • IC nerves lie deep to internal and external intercostal muscles, and superficial to intercostalis intimis and the pleura.  The neurovascular bundle lies immediately inferior to the rib and consists of vein, artery and nerve (superior to inferior)
    • Method
      • Feel for the posterior angle of the rib at around the posterior axillary line and insert the needle at or just under the rib, ‘walking’ down the rib if necessary.  Once there, only advance 2-5mm more before infiltrating (aspirate beforehand to ensure not in IC vein/artery)

See also spinal and epidural

Spinal Anaesthesia


  • Surgical procedures to the lower body
  • Analgesia for upper abdominal surgery (used in combination with GA)


  • Relative
    • Aortic/mitral stenosis
      • Because the spinal block also blocks the sympathetic nerves, vasodilation occurs below the level of block, causing hypotension.  In stenosis, the heart may not be able to compensate (fixed output).
    • Systemic sepsis
  • Absolute
    • Localised sepsis
    • Anticoagulated patient


  • Spinal cord terminates at L1/2 in adults (lower in children).  The dura/subarachnoid space ends at S2 in adults.
    • Spinal anaesthesia is infiltrated in the CSF surrounding the spinal cord.  To avoid injury to the spinal cord, needles are usually inserted between these levels.
  • Surface anatomy
    • Iliac crests -> L3/4
    • PSIS -> S2
  • Skin – subcutaneous tissue – supraspinous ligament – ligamentum flavum – dura


  • The patient should be sitting or lying on their side
    • Back flexion opens the intervertebral spaces.
  • Clean the back using antiseptic solution.  Adopt an aseptic approach to the procedure.
  • Aim to identify the L3/4, L4/5 or L5/S1 interspace (use the iliac crest as a landmark).
  • The spinal needle is inserted in the midline, aiming slightly cranially.
    • Resistance increases as the ligamentum flavum is entered and when the dura is encountered, with a sudden “give” as the dura is pierced.
    • Correct placement of the needle is confirmed by cerebrospinal fluid at the hub.
  • Inject the local anaesthetic
    • Note only a small amount is required (usually Bupivacaine 0.5% 1.2mls or 15 micrograms of fentanyl)
  • Monitoring
    • Make sure to monitor BP and HR closely, as well as any blood loss (usually requires fluid resuscitation)
    • Rarely, if the anaesthetic spreads to the brainstem, the patient may experience decrease in conscious level, dysphonia, dyspnoea etc.
    • More commonly, headache may occur due to transient decrease in the ICP after puncture of the dura.
    • Patients should also be catheterised (urinary retention is not uncommon)

Pre-operative Counselling and Consent


  • Discuss the diagnosis and treatment options at a time and place at which the patient is best able to understand and retain the information.
  • Where possible, explain the up to date, relevant information in a way that the patient will understand; and allow time for the patient to process information and ask any questions
  • You should not present information in a way that might influence patients’ decision making- explain the options fully
  • Make sure to document what was said and decided.  Most cases will also require a separate consent form to be signed.
    • Emphasis that signing a consent form is not final and decision can be reversed at any time.

Note that new consent laws state that you should inform the patient of risks which are ‘material’ to the patient i.e. which are important to them regardless of the likelihood of it happening.  You should, therefore, inform patients not just of common potential risks, but those that might impacts on them most (note that most of these would be in both categories, though some may not).

Types of consent forms

  1. Patient able to consent for themselves
  2. Those requiring parental consent
  3. Those requiring parental consent BUT where the procedure does not involve loss of consciousness
  4. Patients who lack capacity.


  • WIPE (wash hands, introduce, gain permission, explain the basis for discussion)
  • Points to cover
    • Diagnosis; current symptoms; prognosis if left untreated
    • Alternative options for treatment/investigation (including not to treat)
    • The purpose of proposed treatment; what it will entail (e.g. duration, procedure)
    • How the patient should prepare (including medication management)
    • Risks/side effects as well as benefits (include probabilities where possible)
    • What will happen after (short and long-term)
    • Who will be involved (and who is responsible for what; include also any students)
  • It is good to check that the patient has understood everything (/what the patient wishes/does not wish to know)
    • Ask them if they have any concerns/questions
    • Ask them, if possible, to describe the procedure to you
  • Provide written information where possible.

Common complications/risks/side effects

  • Infection
    • Wound site
    • Post op HAP (chest, urinary)
  • Pain
  • Bleeding (during and post-operatively)
  • Thrombosis (usually post op)
  • Complications of anaesthetic (e.g. N&V; confusion; disorientation)

Clotting/Coagulation Screen and Interpretation

Clotting/Coagulation screens can be important:

  • In identifying haematological conditions/dysfunction, as well as other systems (in particular, liver dysfunction)
  • In monitoring response to and modifying treatments (in particular, warfarin and heparin)
  • In the work-up of patients who are having invasive procedures (classically surgery, but anything more invasive than venepuncture may require screening)

Most screens measure

  • Prothrombin time (PT; normally 11-13 sec)
  • INR (International normalised ratio; normally 1)
    • INR is essentially a comparison of the patient’s PT against a control PT
    • It can be useful as it varies little between labs and tests, making it particularly good for monitoring a trend in patients PT (e.g. with warfarin use)
  • Activated Partial Thromboplastin Time (aPTT; normal values vary)
    • Measures the time taken for a clot to form when exposed to coagulation factors of the Intrinsic pathway
  • Fibrinogen (1.5-4g/l)

Prolonged PT

  • Vitamin K antagonists e.g. warfarin; or vitamin K deficiency
  • Liver disease (causes a reduction in the production of Vit K dependent clotting factors)
    • Often used as a marker of liver dysfunction in paracetamol overdose
  • DIC

Prolonged aPTT

  • Unfractionated heparin and some other anticoagulants (e.g. fondaparinux)
  • Severe liver disease
  • DIC
  • Von Willebrand disease
  • Haemophilia (A or B)
  • Other rare coagulation factor deficiencies
  • SLE/Antiphospholipid syndrome

Interpretation of U&Es


  • Sodium is commonly a marker of fluid balance (the major solute responsible for osmotic water movements)
    • Hypernatraemia
      • Usually secondary to dehydration.  Rarer causes include diabetes indipidus, salt poisoning
    • Hyponatraemia
      • Usually secondary to fluid overload (causing dilution of Na in the blood).  Often this can be a side effects of drugs, but other causes e.g. SIADH, may cause this


  • Potassium is crucial to the normal functioning of cells (particularly cells of the heart)
    • Hyperkalaemia is often secondary to drugs, haemolysis or renal impairment.
    • Hypokalaemia is often due to drugs, but can be secondary to potassium loss from the gut e.g. diarrhoea, or kidneys

Urea and Creatinine

  • Urea is a breakdown product of blood.  Creatinine is another breakdown product released by muscle.  They are both filtered by the kidneys.
  • A raised urea with a normal creatinine suggests a non-renal cause of hyperuraemia
    • Most commonly dehydration; more rarely, GI bleeds can cause a raised urea
  • A high urea with a raised creatinine suggests renal impairment (acute or chronic)