Lignocaine (Lidocaine) - Barash, Cullen & Stoelting's Clinical Anesthesia, 9e

1. Chemical Classification & Structure

• Chemical class: Aminoamide
• Exists as a racemic mixture (in contrast to ropivacaine and levobupivacaine, which are single enantiomers)

2. Physicochemical Properties

3. Mechanism of Action

Voltage-Gated Sodium Channel Blockade

Critical Length for Block ("Decremental Conduction")

• Only ~1-2% of injected drug ultimately penetrates the nerve
• Desheathed nerves in vitro need ~0.7-0.9 mM lidocaine; in vivo, 2% lidocaine (= 75 mM) is used clinically because of the perineural sheath barrier
• Block requires both adequate concentration (to exceed the minimum blocking concentration) and adequate volume (to cover a critical length of nerve fiber)
• According to the model of decremental conduction (Fig. 22-7), action potentials can "skip" over a short blocked segment - requiring exposure over a sufficient nerve length to cause extinction

Use-Dependent (Phasic) Blockade

Differential Nerve Block

4. Pharmacokinetics

Key Parameters (Table 22-7)

Systemic Absorption

1. Site of injection (intercostal > epidural > brachial plexus > subcutaneous)
2. Dose administered
3. Drug's intrinsic pharmacokinetic properties
4. Addition of a vasoconstrictor (epinephrine)

Protein Binding

Metabolism

Special Populations

• Very young and elderly: decreased clearance and increased absorption
• Pregnancy: may decrease clearance
• Cardiac disease: altered pharmacokinetics - lower doses required
• Hepatic disease: markedly reduced clearance - reduce doses significantly

5. Additives that Enhance Lidocaine Activity

Epinephrine

• Produces local vasoconstriction, reducing vascular absorption
• Prolongs duration of block
• Reduces peak plasma concentration (Cmax)
• Clinically, adding epinephrine 5 µg/mL to lidocaine markedly improves the quality and duration of epidural and spinal anesthesia

Alkalinization (Sodium Bicarbonate)

Dexamethasone

Alpha-2 Agonists (Clonidine)

• Multiple mechanisms: supraspinal and spinal adrenergic receptors + direct inhibitory effects on peripheral A and C fibers
• Adds ~2 hours to block duration regardless of whether an intermediate- or long-acting LA is used

6. Clinical Uses

6a. Spinal (Intrathecal) Anesthesia

6b. Epidural Anesthesia

6c. Peripheral Nerve Blocks

6d. IV Lidocaine (Intravenous)

• Used as a perioperative analgesic infusion, particularly for abdominal surgery
• The 5% lidocaine patch delivers lidocaine locally at the site of neuropathic pain (e.g., post-herpetic neuralgia) - analgesia by local sodium channel blockade, not systemic effect
• IV lidocaine should not be infused concurrently with other local anesthetics (including peripheral nerve blocks or topical lidocaine patches) due to additive LAST risk

6e. Antiarrhythmic Use (Class IB)

• Depresses automaticity by reducing the slope of phase 4 depolarization
• Reduces the heterogeneity of ventricular refractoriness
• Tends to reverse the reduction in ventricular fibrillation (VF) threshold caused by ischemia/infarction

• Initial bolus: 1 to 1.5 mg/kg IV
• Additional boluses: 0.5 to 0.75 mg/kg every 5-10 minutes during CPR
• Maximum total dose: 3 mg/kg
• Used when VF/pulseless VT is refractory to defibrillation and amiodarone is unavailable
• Amiodarone is preferred (more evidence); lidocaine is an alternative with few side effects

7. Dose-Dependent Systemic Effects (Table 22-11)

8. CNS Toxicity (LAST - Local Anesthetic Systemic Toxicity)

• CNS disturbances are prominent in ~80-90% of LAST cases
• Most frequent manifestations: seizures, agitation, loss of consciousness
• Commonly preceded by prodromal signs: perioral paresthesia ("numbness of tongue"), metallic taste (peragusia), tinnitus, lightheadedness
• Concomitant cardiovascular derangements in ~half of cases
• The potential for CNS toxicity correlates directly with lipid solubility/potency - lidocaine is less toxic than bupivacaine on a mg-for-mg basis
• Factors that increase CNS toxicity risk: decreased protein binding, reduced clearance, systemic acidosis, hypercapnia
• Factors that reduce seizure risk: coadministration of benzodiazepines or barbiturates (CNS depressants)

9. Cardiovascular Toxicity

• CVS toxicity occurs at plasma concentrations far greater than CNS toxicity - CVS:CNS ratio for lidocaine is ~7.1 (vs. 2.0 for bupivacaine)
• This makes lidocaine significantly safer than bupivacaine from a cardiovascular standpoint
• All LAs can cause hypotension, dysrhythmias, and myocardial depression - but lidocaine is much less likely than bupivacaine/ropivacaine to cause cardiovascular collapse or complete heart block
• Mechanism: blocks cardiac Nav1.5 sodium channels, with additional effects on calcium and potassium currents

10. Management of LAST (Table 22-13 - ASRA Practice Advisory)

1. Stop injection of local anesthetic immediately
2. Airway management: secure airway, ventilate with 100% O2; prevent hypoxia, hypercapnia, acidosis
3. 20% Lipid Emulsion (Intralipid):
   • Bolus over 2-3 min: 100 mL (>70 kg) or 1.5 mL/kg (<70 kg)
   • Follow with infusion over 15-20 min: 200-250 mL (>70 kg) or 0.25 mL/kg/min (<70 kg)
   • Can repeat bolus and increase infusion to 0.5 mL/kg/min if instability continues
   • Maximum initial dose: 12 mL/kg
4. Seizure management: benzodiazepines; small dose succinylcholine for intractable seizures (to minimize acidosis)
5. Modified ACLS:
   • Small doses of epinephrine (<1 mcg/kg)
   • Amiodarone for ventricular arrhythmias
   • AVOID: vasopressin, calcium channel blockers, beta blockers, or additional local anesthetics
6. Alert facility with cardiopulmonary bypass capability if instability persists
7. Monitor for at least 2-6 hours after resolution of symptoms

11. Transient Neurologic Symptoms (TNS) after Spinal Lidocaine

• Incidence: 4% to 40% in prospective randomized studies - far higher than with other spinal agents
• Symptoms: pain or sensory abnormalities in the lower back, buttocks, or lower extremities appearing within 24 hours of resolution of spinal block and resolving within 72 hours
• TNS is significantly more common with lidocaine than with bupivacaine, prilocaine, or procaine (Table 22-14)
• This has led to a significant decline in the use of spinal lidocaine for short procedures, with many centers switching to chloroprocaine, prilocaine, or low-dose bupivacaine

12. Differential Toxicity Summary (CVS:CNS Ratio)

Key Points (Barash-Stoelting Summary on Lidocaine)

1. Prototype aminoamide local anesthetic; intermediate potency and duration
2. Mechanism: intracellular binding to voltage-gated Na+ channels; use-dependent blockade
3. pKa 7.9; 65% protein-bound; Vd 1.3 L/kg; T1/2 1.6 h; hepatic metabolism (CYP450)
4. Intermediate lipid solubility means faster onset than bupivacaine but shorter duration
5. Dose-dependent CNS effects: analgesia (1-5 mcg/mL) → seizures (10-15) → CV collapse (>25)
6. CVS:CNS ratio ~7.1 = much safer cardiovascular profile than bupivacaine
7. Antiarrhythmic (Class IB): reduces phase 4 slope, reverses ischemia-induced VF threshold reduction; dose 1-1.5 mg/kg bolus in arrest (max 3 mg/kg); inferior to amiodarone
8. TNS incidence 4-40% with spinal lidocaine - major clinical limitation; has largely been replaced for intrathecal use
9. LAST treatment: stop drug → 100% O2 → 20% lipid emulsion → seizure Rx → modified ACLS (low-dose epi, amiodarone; avoid bupivacaine antagonists)
10. IV lidocaine infusion used for perioperative analgesia; do not combine with other LAs due to additive LAST risk

• Barash, Cullen, and Stoelting's Clinical Anesthesia, 9e, Chapter 22 (Local Anesthetics), pp. 1671-1726
• Barash, Cullen, and Stoelting's Clinical Anesthesia, 9e, Chapter 58 (Cardiac Resuscitation), pp. 4920-4922