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LDS Part 1 (RCS England)

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7.1 Local Anaesthetics, Dosing, Vasoconstrictors & Toxicity

Key Takeaways

  • Maximum recommended doses for healthy adults: Lidocaine 2% with 1:80,000 adrenaline is 4.4 mg/kg (max 300 mg total / ~7 cartridges for 70 kg adult); Articaine 4% with 1:100,000 adrenaline is 7.0 mg/kg (max 500 mg / ~5.6 cartridges); Prilocaine 3% with felypressin 0.03 IU/ml is 6.0 mg/kg (max 400 mg).
  • Local anaesthetics block voltage-gated sodium channels (Nav1.5) from the intracellular side of the neuronal membrane, preventing depolarization and nerve impulse conduction. Amides undergo hepatic metabolism, whereas Articaine undergoes 90% plasma esterase hydrolysis, giving it a remarkably short elimination half-life of 20-30 minutes.
  • Vasoconstrictors prolong analgesia, reduce systemic toxicity, and provide surgical haemostasis; however, adrenaline is limited to a maximum of 2 cartridges (0.04 mg) or avoided in severe unstable angina, recent MI (< 6 months), uncontrolled hyperthyroidism, phaeochromocytoma, and in patients taking non-selective beta-blockers or TCAs.
  • Prilocaine metabolism generates o-toluidine, which oxidizes hemoglobin to methemoglobin; methemoglobinemia (> 10-15% levels) presents as cyanosis unresponsive to oxygen and chocolate-brown blood, requiring treatment with intravenous methylene blue (1-2 mg/kg).
  • Local Anaesthetic Systemic Toxicity (LAST) presents with early CNS excitation (circumoral paresthesia, metallic taste, tinnitus, twitching) progressing to CNS depression (seizures, coma) and cardiovascular collapse; emergency management requires stopping administration, BLS/ALS, 100% oxygen, seizure control with midazolam, and Intralipid 20% lipid emulsion therapy (1.5 mL/kg IV bolus over 1 min, then 0.25 mL/kg/min infusion).
Last updated: July 2026

7.1 Local Anaesthetics, Dosing, Vasoconstrictors & Toxicity

Local anaesthesia forms the cornerstone of pain control in clinical dentistry. A thorough understanding of local anaesthetic pharmacology, safe dosage calculations, vasoconstrictor dynamics, and emergency management of systemic toxicity is mandatory for the Royal College of Surgeons LDS Part 1 examination and safe UK dental practice.

Chemical Structure & Mechanism of Action

Local anaesthetic agents are amphiphilic molecules comprising a lipophilic aromatic ring, an intermediate chain (containing either an ester or amide linkage), and a hydrophilic tertiary amine group.

Classification

  • Amides: Contain an amide linkage (-NH-CO-). Examples include lidocaine, articaine, prilocaine, mepivacaine, and bupivacaine. A useful mnemonic is that amide agents contain the letter "i" twice in their generic name (e.g., lidocaine).
  • Esters: Contain an ester linkage (-CO-O-). Examples include procaine, tetracaine, and benzocaine. Esters are metabolized in plasma by pseudocholinesterase (plasma cholinesterase) and yield para-aminobenzoic acid (PABA), a metabolite strongly associated with allergic hypersensitivity reactions. Esters are rarely used for injectable dental anaesthesia in the UK today.

Mechanism of Nerve Blockade

Local anaesthetics act by reversibly blocking voltage-gated sodium channels ($Na_v1.5$) along the neuronal cell membrane (the axolemma):

  1. Membrane Penetration: In their uncharged, un-ionized base form ($LA$), local anaesthetic molecules diffuse across the lipophilic nerve sheath and neuronal membrane into the intracellular axoplasm.
  2. Intracellular Ionization: Within the axoplasm (pH ~7.2), the un-ionized base combines with hydrogen ions to form charged, ionized cations ($LA · H^+$).
  3. Channel Receptor Binding: The charged cation binds specifically to a receptor site located within the internal vestibule of the open or inactivated voltage-gated sodium channel.
  4. Inhibition of Depolarization: Binding physically plugs the sodium pore, preventing influx of $Na^+$ ions down their electrochemical gradient. This arrests the generation of the resting membrane potential depolarization required to reach threshold potential, halting the propagation of action potentials along nociceptive A-$delta$ and C nerve fibres.
ightleftharpoons quad ext{LA} ; + ; ext{H}^+$$ ### Physicochemical Factors Governing Clinical Activity - **Dissociation Constant ($pKa$)**: The $pKa$ is the pH at which 50% of the drug exists in the un-ionized base form and 50% in the ionized cationic form. Tissue pH in healthy oral mucosa is 7.4. Local anaesthetics with a $pKa$ closer to physiological pH (e.g., mepivacaine $pKa$ 7.6, lidocaine $pKa$ 7.9) have a higher ratio of un-ionized base at physiological pH, allowing rapid nerve sheath penetration and yielding a **faster onset of action**. In inflamed or infected tissue (pH ~5.5 to 6.0), the acidic microenvironment shifts the equilibrium heavily toward the ionized cationic form ($LA · H^+$), reducing membrane penetration and leading to **anaesthetic failure**. - **Lipid Solubility**: Correlates directly with **intrinsic anaesthetic potency**. Highly lipid-soluble agents (e.g., bupivacaine) penetrate nerve membranes more efficiently at lower concentrations. - **Protein Binding**: Correlates directly with **duration of action**. Agents with high affinity for membrane proteins (e.g., bupivacaine 95% protein-bound) remain attached to sodium channel proteins longer than weakly bound agents (e.g., lidocaine 65% bound). --- ## Pharmacokinetics & Specific Local Anaesthetic Agents In UK dental practice, local anaesthetics are supplied in standardized pre-filled glass cartridges (typically **2.2 mL** in volume). ### Lidocaine Hydrochloride (2% with 1:80,000 Adrenaline) - **Gold Standard Amide**: Lidocaine remains the baseline comparator for dental local anaesthesia. Formulated as a 2% solution (20 mg/mL) with 1:80,000 adrenaline (12.5 $mu$g/mL). - **Cartridge Content**: A 2.2 mL cartridge contains **44 mg lidocaine** and **27.5 $mu$g adrenaline**. - **Dosing**: Maximum recommended dose is **4.4 mg/kg** up to an absolute maximum of **300 mg** in a healthy adult (~7 cartridges for a 70 kg individual). - **Metabolism**: Hepatic metabolism via cytochrome P450 enzymes (CYP1A2 and CYP3A4) into active metabolites (monoethylglycinexylidide). Elimination half-life ($t_{1/2}$) is ~90 minutes. ### Articaine Hydrochloride (4% with 1:100,000 or 1:200,000 Adrenaline) - **Hybrid Amide-Ester Structure**: Articaine possesses a thiophene ring instead of a benzene ring (increasing lipid solubility) and an additional ester group. - **Metabolic Profile**: Hydrolyzed **90% in plasma** by plasma carboxylesterases to an inactive metabolite (articainic acid), with only 10% cleared by hepatic CYP450. Consequently, its elimination half-life is exceptionally short (**20–30 minutes**), minimizing systemic drug accumulation during prolonged procedures. - **Cartridge Content**: A 2.2 mL cartridge of 4% articaine contains **88 mg articaine**. - **Dosing**: Maximum recommended dose is **7.0 mg/kg** up to an absolute maximum of **500 mg** (~5.6 cartridges for a 70 kg individual). - **Clinical Considerations**: Excellent soft tissue and bony diffusion. Highly effective for buccal infiltration in mandibular adult molars. Due to a historically reported risk of paresthesia, current UK guidelines recommend avoiding 4% articaine for inferior alveolar nerve blocks (IANB), reserving it primarily for infiltration techniques. ### Prilocaine Hydrochloride (3% with 0.03 IU/mL Felypressin or 4% Plain) - **Pharmacological Features**: Secondary amide with lower systemic toxicity than lidocaine. - **Vasoconstrictor**: Combined with **felypressin** (0.03 IU/mL), a synthetic vasopressin ($V_1$) analogue that causes venous smooth muscle constriction without cardiac adrenergic stimulation. - **Cartridge Content**: A 2.2 mL cartridge of 3% prilocaine contains **66 mg prilocaine**. - **Dosing**: Maximum recommended dose is **6.0 mg/kg** up to an absolute maximum of **400 mg**. - **Methemoglobinemia Risk**: Hepatic and pulmonary metabolism of prilocaine produces **$o$-toluidine**. $o$-toluidine oxidizes ferrous iron ($Fe^{2+}$) in hemoglobin to ferric iron ($Fe^{3+}$), producing **methemoglobin**, which cannot reversibly bind oxygen. When methemoglobin levels exceed 10–15%, cyanosis unresponsive to 100% oxygen occurs. Emergency treatment is intravenous **methylene blue (1–2 mg/kg)**. - **Pregnancy Warning**: Felypressin exhibits oxytocic activity and may induce uterine contractions; prilocaine with felypressin is contraindicated in pregnant patients. ### Mepivacaine Hydrochloride (3% Plain) - **Pharmacological Features**: Tertiary amide with mild intrinsic vasoconstrictive properties. - **Cartridge Content**: A 2.2 mL cartridge contains **66 mg mepivacaine**. - **Dosing**: Maximum recommended dose is **4.4 mg/kg** up to an absolute maximum of **300 mg**. - **Clinical Indication**: Ideal for patients in whom adrenergic vasoconstrictors are contraindicated (e.g., severe cardiovascular disease, brittle hyperthyroidism). ### Bupivacaine Hydrochloride (0.5% with 1:200,000 Adrenaline) - **Long-Acting Amide**: High lipophilicity and 95% protein binding provide prolonged pulpal (up to 1.5 hours) and soft tissue anaesthesia (up to 8 hours). - **Dosing**: Maximum recommended dose is **2.0 mg/kg** up to an absolute maximum of **150 mg**. - **Cardiotoxicity Warning**: Dissociates very slowly from cardiac sodium channels during diastole ("slow-in, slow-out"). Accidental intravascular injection precipitates refractory re-entrant ventricular arrhythmias, electromechanical dissociation, and cardiac arrest. --- ## Comparison of Dental Local Anaesthetic Agents | Agent | Conc. (%) | Vasoconstrictor | Max Dose (mg/kg) | Absolute Max (mg) | Cartridge Content (2.2 mL) | Elimination $t_{1/2}$ | |---|---|---|---|---|---|---| | **Lidocaine** | 2% | Adrenaline 1:80,000 | 4.4 mg/kg | 300 mg | 44 mg | ~90 mins | | **Articaine** | 4% | Adrenaline 1:100,000 | 7.0 mg/kg | 500 mg | 88 mg | ~20–30 mins | | **Prilocaine** | 3% | Felypressin 0.03 IU/mL | 6.0 mg/kg | 400 mg | 66 mg | ~90 mins | | **Mepivacaine** | 3% | Plain (None) | 4.4 mg/kg | 300 mg | 66 mg | ~110 mins | | **Bupivacaine** | 0.5% | Adrenaline 1:200,000 | 2.0 mg/kg | 150 mg | 11 mg | ~210 mins | --- ## Vasoconstrictors & Clinical Contraindications Vasoconstrictors are added to local anaesthetic solutions to counteract intrinsic local anaesthetic vasodilation. They retard systemic absorption, reduce peak blood concentrations (lowering systemic toxicity risk), prolong depth and duration of anaesthesia, and provide local surgical haemostasis. ### Adrenaline (Epinephrine) - **Mechanism**: Endogenous catecholamine acting on $alpha_1$ (vascular smooth muscle constriction), $eta_1$ (positive inotropy and chronotropy in myocardium), and $eta_2$ (bronchodilation and skeletal muscle vasodilation) adrenergic receptors. - **Concentrations**: 1:80,000 = 12.5 $mu$g/mL; 1:100,000 = 10 $mu$g/mL; 1:200,000 = 5 $mu$g/mL. - **Safe Dose Limits in Cardiac Disease**: In patients with severe cardiovascular disease, restrict adrenaline to a **maximum of 2 cartridges of 1:80,000 solution (0.04 mg adrenaline)** per visit. - **Absolute / Relative Contraindications**: - Severe unstable angina or recent myocardial infarction (< 6 months). - Refractory cardiac dysrhythmias. - Uncontrolled severe hypertension ($> 180/110$ mmHg). - Uncontrolled hyperthyroidism (thyrotoxicosis risk). - Phaeochromocytoma (catecholamine-secreting tumor). - Patients taking **non-selective beta-blockers** (e.g., propranolol): Blockade of $eta_2$ vasodilatory receptors leaves $alpha_1$ vasoconstriction unopposed, triggering severe **hypertensive crisis** accompanied by compensatory **reflex bradycardia**. - Patients taking **Tricyclic Antidepressants (TCAs)** (e.g., amitriptyline): TCAs inhibit neuronal monoamine reuptake, potentiating exogenous adrenaline and increasing dysrhythmia risk (2- to 4-fold pressor enhancement). --- ## Local Anaesthetic Systemic Toxicity (LAST) Local Anaesthetic Systemic Toxicity is a life-threatening medical emergency caused by accidental direct intravascular injection or administration of excessive total dosage leading to toxic plasma drug levels. ### Clinical Presentation LAST typically displays a biphasic progression affecting the Central Nervous System (CNS) followed by the Cardiovascular System (CVS): 1. **Initial CNS Excitation**: Lightheadedness, circumoral paresthesia, numbness of the tongue, metallic taste, tinnitus, hyperacusis, visual disturbances, anxiety, agitation, facial muscular twitching, and tremor. 2. **Severe CNS Depression**: Generalized tonic-clonic seizures, loss of consciousness, respiratory depression, and respiratory arrest. 3. **Cardiovascular Toxicity**: Initial transient hypertension and tachycardia, rapidly progressing to myocardial depression, conduction delays (PR and QRS prolongation), severe hypotension, ventricular dysrhythmias (ventricular tachycardia, ventricular fibrillation), and asystole. ### Emergency Management Protocol (AAGBI / RCUK Guidelines) - **IMMEDIATE ACTION**: Stop injecting local anaesthetic immediately. Call emergency medical services (**999**) and request resuscitation support. - **Airway & Oxygenation**: Secure the airway and deliver **100% high-flow oxygen**. Hyperventilate the patient: correcting arterial hypoxemia and hypercapnia is vital, as acidosis increases un-ionized local anaesthetic fraction and lowers the seizure threshold. - **Seizure Control**: Administer intravenous **midazolam (2.5–5 mg)** or lorazepam to abort seizures. - **Antidotal Therapy — Intralipid 20% Lipid Emulsion**: - **Lipid Sink Theory**: Intralipid creates an intravascular lipid phase that extracts lipophilic local anaesthetics from cardiac and cerebral tissues. - **Initial Bolus**: Administer an immediate IV bolus of **20% Intralipid at 1.5 mL/kg over 1 minute** (~100 mL for a 70 kg adult). - **Continuous Infusion**: Start an IV infusion of **20% Intralipid at 0.25 mL/kg/min** (~18 mL/min for 70 kg). - **Repeat Bolus**: Repeat the bolus once or twice at 5-minute intervals if cardiovascular stability is not restored, and double the infusion rate to 0.5 mL/kg/min.
Test Your Knowledge

What is the maximum recommended dose of lidocaine 2% with 1:80,000 adrenaline in a healthy adult patient, and how many standard 2.2 mL cartridges does this equate to for a 70 kg individual?

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Test Your Knowledge

Which local anaesthetic metabolic property uniquely distinguishes articaine from other amide local anaesthetics, giving it a significantly shorter elimination half-life?

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Test Your Knowledge

What is the first-line intravenous lipid emulsion dose and administration protocol for managing Local Anaesthetic Systemic Toxicity (LAST) in a 70 kg cardiac arrest patient?

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