Table Of Contents
Local Anaesthetics
Local anesthetics provide analgesia and anaesthesia by disrupting the conduction of impulses along nerve fibers. They block voltage-gated Na+, thus inhibiting the influx of sodium and preventing an action potential from being reached. They are weak bases in equilibrium (pKa > 7.4). Anaesthetics with pKa closer to physiologic pH have a greater fraction of non-ionized form (that can cross the plasma membrane) and thus have a faster onset. Conversely, in acidic environments e.g. infection, pKa is further from the environmental pH and the anaesthetic will have a slower onset.
Characteristics of Local Anaesthetics
| Characteristic | Association |
|---|---|
| Speed of onset | pKa (degree of ionization), Concentration |
| Potency | Lipid solubility |
| Duration of action | Protein binding (alpha-1 amino glycoprotein binds drug and carries it away for metabolism) |
Categories of local anaesthetics
| Category | Drugs | Metabolism |
|---|---|---|
| Amides (i before-caine) | lidocaine, Bupivacaine, Ropivacaine, Mepivacaine, Etidocaine, Levobupivacaine | Liver metabolism (aromatic hydroxylation, N-dealkylation, amide hydrolysis). Methylparaben used as a preservative is metabolized into PABA which can cause a small allergic-type reaction in patients. |
| Esters | Cocaine, Chloroprocaine, Procaine, Tetracaine | Plasma pseudocholinesterase and RBC esterase (hydrolysis at ester linkage) |
Amide Local Anaesthetics
| Amides | pKa | Onset | Max dose (mg/kg) | Max dose with Epinephrine (mg/kg) |
|---|---|---|---|---|
| Lidocaine | 7.9 | Rapid | 4.5 | 7 |
| Mepivacaine | 7.6 | Medium | 5 | 7 |
| Prilocaine | 7.9 | |||
| Bupivacaine | 8.1 | Slow | 2.5 | 3 |
| Ropivacaine | 8.1 | Slow | 1.5 | N/A |
Ester Local Anaesthetics
| Esters | pKa | Onset | Max dose (mg/kg) | Max dose with Epi (mg/kg) |
|---|---|---|---|---|
| Procaine | 8.9 | |||
| Chloroprocaine | 8.7 | Rapid | 10 | 15 |
| Tetracaine | 8.5 | Slow | 1.5 | N/A |
Peripheral block Duration
| Local Anaesthetic | Duration (hours) |
|---|---|
| Lidocaine | 2-4 |
| Mepivacaine | 3-5 |
| Ropivacaine | 5-8 |
| Bupivacaine | 6-12 |
- Structure of local anaesthetic Has 3 major chemical moieties
- Lipophilic aromatic benzene ring
- Ester or Amide linkage
- Hydrophilic tertiary amine
- Mechanism of action
- Non-ionized (base, lipid-soluble) form crosses the neuronal membrane
- Re-equilibration in axoplasm between the 2 forms
- The ionized (cationic, water-soluble) form binds to the intracellular alpha subunit of the Na+ channel
- Routes of administration
- Topical
- Intravenous
- To inhibit inflammation
- To decrease hemodynamic response to laryngoscopy
- To decrease post-op pain and opioid consumption
- Reduces MAC requirement by 40%
- Epidural
- Intrathecal (spinal)
- Perineural (regional): sensory loss precedes motor weakness since small diameter A-delta myelinated nerves are most susceptible
- Why does chloroprocaine have a fast onset despite its pKa?
- Chloroprocaine is used in relatively higher concentrations because of its low systemic toxicity (it is rapidly metabolized by pseudocholinesterase)
- Which is the longest acting local anaesthetic
- Bupivacaine
- Why is Ropivacaine preferred over Bupivacaine?
- Has less cardiotoxicity
Local Anaesthetic Systemic Toxicity (LAST)
LAST is caused by systemic absorption at the injection site. The rate and extent of systemic absorption depend on the dose, the drug’s intrinsic pharmacokinetic properties, and the addition of vasoactive agents e.g. Epinephrine
Incidence (ICEBALLS): IV > tracheal > Intercostal > Caudal > Epidural > Brachial plexus > Axillary > Lower extremity (Sciatic/femoral) > Subcutaneous
- CNS toxicity (readily crosses the BBB)
- Lightheadedness, tinnitus, tongue numbness, metallic taste → CNS excitation (inhibitory pathways are blocked) → CNS depression, seizures → Coma
- Cardiovascular toxicity (dose-dependent)
- Bradycardia, Ventricular arrhythmia → Decreased contractility → Circulatory arrest
- Which local anesthetic is the most cardiotoxic?
- Bupivacaine: it has high binding to resting or inactivated Na+ channels and slower dissociation from these channels during diastole
- Treatment of LAST
- Stop the local anaesthetic
- Call for help + intralipid kit
- Supportive Treatment
- Airway management, Breathing, and Circulatory Support
- Circulatory support using vasopressors e.g. epinephrine, phenylephrine, and norepinephrine. Reduce individual epinephrine doses to < 1mcg/kg
- Benzodiazepines for seizure including Midazolam 3-10mg, Diazepam 5 – 15mg, Propofol 20-60mg. Propofol and Thiopental are not not preferred due to their cardiac depressant effects.
- Manage Arrhythmias according to ACLS protocol. Avoid Lidocaine as an anti-arrhythmic.
- Neuromuscular blockers in case of ongoing muscle contraction due to refractory tonic-clonic movement
- Mechanical chest compression device or a cardiac bypass may be indicated in bupivacaine-induced LAST
- Specific Treatment: Intravenous fat emulsion therapy (acts as a lipid sink and helps redistribute the local anaesthetic away from target organs)
- Bolus 1.5cc/kg of 20% intralipid IV (maximum of 3 boluses)
- Infusion 0.25cc/kg/min (max rate 0.5cc/kg/min)
- Given as simultaneous boluses and infusion based on ideal body weight.
- After 5 minutes a second bolus can be given and the infusion rate doubled if cardiovascular stability has not returned. A 3rd and final bolus can be given after a further 5 minutes if the total maximum dose has not been reached.
- Which medication should be avoided in case of LAST due to their cardiodepressant activity
- VasopressinCalcium channel blockersBeta-blockersLocal anaestheticsPropofol and sodium thiopental
