Anaesthesia

Definition & Mechanism

Local anaesthetics (LAs) are drugs that produce reversible blockade of nerve conduction in a circumscribed area, causing loss of sensation (and, at higher concentrations, motor block) without loss of consciousness. They act by blocking voltage-gated sodium channels in the nerve membrane from the inside, preventing the sodium influx needed to generate and propagate an action potential — so the nerve cannot depolarise and impulse conduction stops.

Structure & Classification

A local anaesthetic molecule has an aromatic (lipophilic) ring and an amine (hydrophilic) group joined by an ester or amide link — and this link classifies them. Esters (procaine, amethocaine/tetracaine, cocaine) are metabolised by plasma cholinesterase and are more likely to cause allergy (a PABA metabolite). Amides (lignocaine, bupivacaine, ropivacaine, prilocaine) are metabolised in the liver and allergy is rare. (A memory aid: amides have an ‘i’ in the prefix — lignocaine, bupivacaine.)

Determinants of Action

Three physicochemical properties govern LA behaviour: pKa determines the speed of onset (agents with a pKa closer to physiological pH have more unionised drug to cross the membrane, so a faster onset); lipid solubility determines potency; and protein binding determines the duration of action. This is why bupivacaine (highly protein-bound, lipid-soluble) is potent and long-acting.

Differential Block

Nerve fibres are blocked in order of size and myelination: small, unmyelinated fibres first. So autonomic (sympathetic) and pain/temperature fibres are blocked before touch, and motor fibres last — producing a differential block in which pain sensation is lost while some motor power may be retained (exploited in labour epidurals).

Reversibility & Onset

An essential property of local anaesthetic block is that it is fully reversible: as the drug is absorbed away from the nerve and its concentration falls, the sodium channels recover and normal conduction returns, leaving no lasting damage when the drugs are used correctly. The onset of block depends on how much of the drug is in its unionised (lipid-soluble) form to cross the nerve sheath and membrane, which is why agents with a pKa nearer physiological pH act faster and why block is slow and unreliable in acidic, infected tissue where more of the drug is trapped in its ionised form. Once inside the cell the drug becomes ionised again to bind the channel, so both forms matter — the unionised form to get in, the ionised form to act.

• LAs reversibly block voltage-gated Na⁺ channels (from inside) → no action potential → conduction stops; consciousness preserved.
• Structure: aromatic ring + amine linked by ester or amide bond.
• Esters (procaine, amethocaine, cocaine): plasma cholinesterase, more allergy; amides (‘-i-caine’): hepatic, rare allergy.
• pKa → onset; lipid solubility → potency; protein binding → duration.
• Work poorly in acidic (infected) tissue; differential block — autonomic/pain before motor.

Overview

Several local anaesthetics are in common use, differing in onset, potency, duration and toxicity, and each has a maximum safe dose that must not be exceeded to avoid systemic toxicity. The choice depends on the block, the duration required, and whether a vasoconstrictor is used.

Lignocaine (Lidocaine)

The most widely used LA: fast onset, moderate duration, versatile (infiltration, nerve blocks, topical, spinal/epidural, IV regional). Maximum 3 mg/kg plain, 7 mg/kg with adrenaline. It is also an antiarrhythmic (class Ib) for ventricular arrhythmias.

Bupivacaine, Ropivacaine & Prilocaine

Bupivacaine is potent and long-acting (ideal for prolonged blocks, epidurals and spinals) but is the most cardiotoxic (max ~2 mg/kg); the single-isomer levobupivacaine and ropivacaine are similarly long-acting but less cardiotoxic, with ropivacaine producing relatively more sensory than motor block. Prilocaine is useful for intravenous regional anaesthesia (least toxic) but in large doses can cause methaemoglobinaemia.

Choosing an Agent

Use lignocaine for a fast onset and shorter procedures, and bupivacaine/ropivacaine/levobupivacaine where a long duration (postoperative analgesia, epidural) is wanted. Prilocaine is preferred for Bier’s block. A vasoconstrictor prolongs and intensifies the block and raises the safe dose (except for bupivacaine).

Toxicity Ranking & Practical Choice

In broad terms the more potent, lipid-soluble and long-acting an agent is, the more toxic it tends to be, so bupivacaine sits at the toxic end and the shorter-acting, less potent agents at the safer end. In everyday practice this shapes the choice: a quick, short procedure needing rapid onset is well served by lignocaine, whereas prolonged surgical anaesthesia or postoperative analgesia calls for a long-acting agent, in which case the reduced cardiotoxicity of levobupivacaine and ropivacaine is a real advantage over racemic bupivacaine. Prilocaine’s low systemic toxicity makes it the traditional choice for intravenous regional anaesthesia, its main drawback — methaemoglobinaemia — appearing only at large doses.

Concentration, Volume & Additives

How a local anaesthetic behaves in practice depends not only on which agent is chosen but on its concentration and volume and on any additives. A higher concentration produces a denser, more profound block including motor block, whereas a lower concentration can give predominantly sensory analgesia while sparing movement, a distinction exploited in labour and postoperative epidural infusions; the volume determines how far the block spreads. Additives such as adrenaline prolong and intensify the block and raise the safe dose, and other adjuncts (for example opioids added to neuraxial solutions) can enhance and prolong analgesia, so the final solution is tailored to the clinical goal rather than being a single fixed preparation.

• Agents differ in onset, potency, duration, toxicity; know the maximum safe dose.
• Lignocaine: fast, versatile, 3 mg/kg (7 with adrenaline); also a class Ib antiarrhythmic.
• Bupivacaine: potent, long-acting, MOST cardiotoxic (2 mg/kg); ropivacaine/levobupivacaine safer.
• Prilocaine: least toxic (Bier’s block) but methaemoglobinaemia in large doses.
• Vasoconstrictor prolongs/intensifies block & raises safe dose (little benefit for bupivacaine).

Definition & Cause

Local anaesthetic systemic toxicity (LAST) is the toxic effect of an excessive plasma concentration of local anaesthetic, from an overdose (exceeding the safe dose) or, more dangerously, accidental intravascular injection. It primarily affects the central nervous system and the cardiovascular system, and can be fatal.

Clinical Features (Progressive)

Toxicity is dose-related and progressive. Early/CNS: circumoral and tongue numbness/tingling, a metallic taste, tinnitus, light-headedness, visual disturbance, slurred speech and agitation — progressing to muscle twitching and convulsions, then CNS depression (drowsiness, coma, respiratory arrest). Cardiovascular (later, more serious): hypotension, arrhythmias, conduction block and cardiovascular collapse — bupivacaine being especially prone to refractory cardiac arrest.

Management

Stop injecting and call for help. Manage ABC: secure the airway, give 100% oxygen, and control convulsions (benzodiazepine). Treat cardiovascular collapse with standard resuscitation (but prolonged CPR may be needed). The specific antidote is intravenous lipid emulsion (‘Intralipid’ / lipid rescue) — a bolus followed by an infusion — which ‘soaks up’ the lipophilic drug from the tissues. Avoid or reduce certain drugs (e.g. use small adrenaline doses) as advised in LAST protocols.

Prevention

LAST is largely preventable: calculate and stay within the maximum dose, aspirate before injecting (to detect intravascular placement), inject slowly in small increments while talking to the patient, use a test dose (often with adrenaline) for large blocks, and use ultrasound guidance where available.

Timing & Vigilance

The presentation of local anaesthetic systemic toxicity varies with how the toxic level arose: an accidental intravascular injection produces sudden, dramatic features within seconds to a minute, often beginning with seizures or collapse, whereas an overdose absorbed from the tissues produces a more gradual onset over minutes as the plasma level climbs, typically heralded by the early neurological warning signs. This is why the injecting clinician talks to the patient throughout a large block, watching for the earliest symptoms, and why monitoring is continued for a period after injection — the peak plasma level from tissue absorption may not be reached until some minutes have passed.

Cardiac Features & Bupivacaine

While the neurological features usually appear first, it is the cardiovascular effects that make local anaesthetic toxicity lethal, and these are worst with bupivacaine, which binds cardiac sodium channels avidly and dissociates from them slowly so that arrhythmias and myocardial depression can be profound and resistant to standard resuscitation. The picture ranges from hypertension and tachycardia early, through bradycardia and conduction block, to ventricular arrhythmias and asystole, and because recovery of the heart depends on the drug leaving the channels, resuscitation may need to be sustained for a long time — which is exactly the situation in which intravenous lipid emulsion, by drawing the drug out of the tissues, can be life-saving.

• LAST: toxic plasma LA level from overdose or intravascular injection; affects CNS & CVS; can be fatal.
• CNS first: perioral tingling, metallic taste, tinnitus → convulsions → CNS depression.
• CVS later/serious: arrhythmias, collapse (bupivacaine especially refractory).
• Manage: stop, ABC, O₂, control seizures, resuscitate; give IV lipid emulsion (Intralipid) early.
• Prevent: stay within max dose, aspirate, inject slowly in increments, test dose, ultrasound.

Absorption & Fate

After injection, a local anaesthetic acts locally but is progressively absorbed into the circulation; it is the peak plasma concentration that determines the risk of systemic toxicity. Absorption depends on the site (vascularity), the dose and concentration, and whether a vasoconstrictor is added. The drug is then metabolised (amides in the liver, esters by plasma cholinesterase) and excreted.

Effect of Injection Site

The more vascular the site, the faster the absorption and the higher the peak plasma level (and toxicity risk). A rough order of decreasing absorption is intercostal > caudal/epidural > brachial plexus > subcutaneous. This is why the maximum safe dose varies with the block, and why intercostal blocks carry a higher toxicity risk.

Vasoconstrictors (Adrenaline)

Adding a vasoconstrictor (adrenaline) to a local anaesthetic causes local vasoconstriction that slows systemic absorption — which prolongs and intensifies the block, reduces the peak plasma level (raising the safe dose), and reduces surgical bleeding. It is most useful with lignocaine (safe dose rises from 3 to 7 mg/kg) and adds little to bupivacaine.

Other Factors

The dose (mass) of drug, its concentration and volume, addition of vasoconstrictor, the site, and patient factors (weight, cardiac output, hepatic function, pregnancy, extremes of age) all influence plasma levels and effect. Onset can be quickened by warming or alkalinising the solution (more unionised drug).

Systemic & Local Balance

Every regional injection sets up a balance between the desired local effect on the target nerve and the unwanted systemic effect of the fraction that is absorbed, and understanding what shifts that balance is the key to safe practice. A larger mass of drug, a higher concentration, a more vascular site and the omission of a vasoconstrictor all push towards higher plasma levels and greater toxicity risk, whereas the smallest effective dose, a less vascular site and the judicious use of adrenaline push the other way. The clinician therefore chooses the lowest dose and concentration that will do the job, at the appropriate site, and adds a vasoconstrictor where it is safe and helpful.

Patient Factors

The same dose of local anaesthetic does not carry the same risk in every patient, because absorption, distribution and elimination all vary with the individual. Reduced hepatic function or blood flow slows the clearance of the amide agents; low plasma protein raises the free, active fraction; the extremes of age and pregnancy alter both pharmacokinetics and sensitivity; and a low cardiac output changes distribution. These factors mean that maximum doses are guides rather than guarantees, and that the dose is reduced in the frail, the very young or old, and those with significant hepatic or cardiac disease.

• Systemic toxicity depends on PEAK plasma level → governed by site vascularity, dose/concentration, vasoconstrictor.
• Absorption: intercostal > epidural/caudal > brachial plexus > subcutaneous.
• Adrenaline slows absorption → longer/denser block, less bleeding, higher safe dose (esp. lignocaine).
• Adrenaline contraindicated in end-artery areas (fingers, toes, penis, nose, ears) — necrosis risk.
• Onset quickened by warming/alkalinising; amides metabolised hepatically, esters by cholinesterase.

Overview

Local anaesthetics can be delivered by many techniques, from numbing the skin surface to blocking whole regions of the body. These regional techniques can provide anaesthesia for surgery and analgesia while avoiding, or supplementing, general anaesthesia — useful in patients unfit for GA and for postoperative pain relief.

Surface, Infiltration & Field Block

Topical/surface anaesthesia: LA applied to mucous membranes or skin (e.g. EMLA cream before cannulation, topical to the airway or eye). Local infiltration: LA injected directly into the tissues to be incised (e.g. suturing a wound). Field block: LA injected around the operative area to block the nerves supplying it.

Nerve & Plexus Blocks

Peripheral nerve block: LA injected around a specific nerve to anaesthetise its territory (e.g. ulnar, femoral, ankle blocks). Plexus block: a whole plexus is blocked (e.g. brachial plexus block for arm surgery). Ultrasound guidance has greatly improved the accuracy and safety of these blocks.

Intravenous Regional Anaesthesia (Bier’s Block)

Bier’s block (IVRA) anaesthetises a limb by injecting LA (usually prilocaine/lignocaine, never bupivacaine) intravenously into a limb exsanguinated and isolated by a tourniquet — the LA diffuses into the tissues to produce anaesthesia while the tourniquet is inflated. It is used for short procedures on the forearm/hand.

Advantages of Regional Techniques

Beyond simply numbing an area, regional techniques carry genuine advantages that explain their popularity: they can provide excellent operating conditions and prolonged postoperative analgesia while avoiding the risks of general anaesthesia — airway instrumentation, the cardiorespiratory depression of general anaesthetic agents, and postoperative nausea and drowsiness — which is particularly valuable in the elderly, the patient with significant comorbidity, and the day-case setting. They can be used as the sole anaesthetic, in combination with general anaesthesia, or purely for analgesia, and the growth of ultrasound guidance has made many nerve and plexus blocks faster, more reliable and safer to perform.

Complications Common to the Techniques

Whatever the specific method, the regional techniques share a set of potential complications that must be anticipated: systemic toxicity from an excessive dose or intravascular injection, direct nerve injury or intraneural injection, bleeding or haematoma at the site, infection, and failure or an incomplete block requiring supplementation or conversion to general anaesthesia. Careful patient selection and consent, aseptic technique, aspiration before injection, incremental dosing with the patient awake enough to report symptoms, and increasingly the use of ultrasound guidance all reduce these risks, and full resuscitation facilities are always available whenever a significant block is performed.

• LA techniques: topical/surface, infiltration, field block, nerve/plexus block, IV regional (Bier’s).
• Provide anaesthesia/analgesia, avoiding or supplementing GA; ultrasound improves nerve blocks.
• EMLA for skin; infiltration for minor surgery; brachial plexus block for arm.
• Bier’s block: exsanguinate + tourniquet + IV prilocaine/lignocaine (NEVER bupivacaine).
• Don’t release the Bier’s tourniquet early — risk of systemic toxicity.