LOCAL ANESTHETICS AND REGIONAL ANESTHESIA Dr Mahmoud Al-mustafa

Local Anesthetics- History 1860 - cocaine isolated from erythroxylum coca Koller - 1884 uses cocaine for topical anesthesia Halsted - 1885 performs peripheral nerve block with local Bier - 1899 first spinal anesthetic Koller also used cocaine powder on floors to anesthetize the noses of Nazi dogs, is credited with saving many lives. Bier also described first PDH.

Local Anesthetics - Definition A substance which reversibly inhibits nerve conduction when applied directly to tissues at non-toxic concentrations Local anesthetics block generation, propagation, and oscillations of electrical impulses in electrically excitable tissue. Mainly by acting on Na channels.

PHARMACOLOGY AND PHARMACODYNAMICS Clinically used local anesthetics consist of lipid-soluble, substituted benzene ring linked to amine group via alkyl chain containing either an amide or ester linkage. • Type of linkage separates local anesthetics into either aminoamides (metabolized in liver) or aminoesters (metabolized in liver or by plasma cholinesterase).

PHARMACOKINETICS Systemic toxicity depends on blood levels of local anesthetic. • End organs of main concern for toxicity are CV and CNS. • Determinants of systemic absorption » Site of injection (intercostal > caudal > brachial plexus > sciatic/femoral) » Dose » Physiochemical properties (lipid solubility, protein binding) » Addition of epinephrine

Local anesthetics - Mechanism Limit influx of sodium, thereby limiting propagation of the action potential. This slide depicts the effect of sodium influx on overall membrane potential. By limiting influx, local anesthetics inhibit the depolarization of the membrane thereby interfering with propagation of the action potential.

Local Anesthetics - Classes Esters

Local anesthetics - Classes Esters Cocaine Chloroprocaine Procaine Tetracaine Amides Bupivacaine Lidocaine Ropivacaine Etidocaine Mepivacaine

Bupivacaine Amide • Infiltration: use 0.25%, fast onset, 2- to 8-hr duration, max dose 175 mg (225 mg with epinephrine) • Peripheral nerve block: use 0.25-0.5%, slow onset, 4- to 12-hr duration, max dose 175 mg (225 mg with epinephrine

Bupivacaine Epidural anesthesia: Use 0.5-0.75%, moderate onset, 2- to 5-hr duration, max dose 175 mg (225 mg with epinephrine) • Spinal anesthesia: Use 0.5-0.75%, fast onset, 1- to 4-hr duration, max dose 20 mg levo (-) bupivacaine less cardiotoxic than racemic bupivacaine, same

Lidocaine Amide • Infiltration: use 0.5-1%, fast onset, 2- to 8-hr duration, max dose 300 mg (500 mg with epinephrine) • Peripheral nerve block: use 1.0-1.5%, fast onset, 1- to 3-hr duration, max dose 300 mg (500 mg with epinephrine)

Lidocaine Epidural anesthesia: use 1.5-2%, fast onset, 1- to 2-hr duration, max dose 300 mg (500 mg with epinephrine) • Spinal anesthesia: use 1.5-2%, fast onset, 0.5- to 1-hr duration, max dose 100 mg • Topical anesthesia: use 4%, fast onset, 0.5- to 1-hr duration, max dose 300 mg • IV regional: Use 0.25-0.5%, fast onset, 0.5-1 hr duration, max dose 300 mg

Ropivacaine Amide • Infiltration: use 0.2-0.5%, fast onset, 2- to 6-hr duration, max dose 200 mg • Peripheral nerve block: use 0.5-1.0%, slow onset, 5- to 8-hr duration, max dose 250 mg • Epidural anesthesia: Use 0.5-1.0%, moderate onset, 2- to 6-hr duration, max dose 200 mg ·       less cariac toxicity than bupivacaine

Local anesthetics - Formulation Biologically active substances are frequently administered as very dilute solutions which can be expressed as parts of active drug per 100 parts of solution (grams percent) Ex.: 2% solution = _2 grams__ = _2000 mg_ = __20 mg__ 100 cc’s 100 cc’s 1 cc

Local Anesthetics - Allergy True allergy is very rare Most reactions are from ester class - ester hydrolysis (normal metabolism) leads to formation of PABA - like compounds Patient reports of “allergy” are frequently due to previous intravascular injections

Local Anesthetics - Toxicity Tissue toxicity - Rare Can occur if administered in high enough concentrations (greater than those used clinically) Usually related to preservatives added to solution Systemic toxicity - Rare Related to blood level of drug secondary to absorption from site of injection. Range from lightheadedness, tinnitus to seizures and CNS/cardiovascular collapse

Local anesthetics - Duration Determined by rate of elimination of agent from site injected Factors include lipid solubility, dose given, blood flow at site, addition of vasoconstrictors (does not reliably prolong all agents) Some techniques allow multiple injections over time to increase duration, e.g. epidural catheter

Local anesthetics - vasoconstrictors Ratios Epinephrine is added to local anesthetics in extremely dilute concentrations, best expressed as a ratio of grams of drug:total cc’s of solution. Expressed numerically, a 1:1000 preparation of epinephrine would be 1 gram epi 1000 cc’s solution 1000 mg epi 1000cc’s solution = 1 mg epi 1 cc

Local anesthetics - vasoconstrictors Therefore, a 1 : 200,000 solution of epinephrine would be 1 gram epi 200,000 cc’s solution 1000 mg epi 200,000 cc’s solution = or 5 mcg epi 1 cc solution

Local anesthetics - vasoconstrictors Vasoconstrictors should not be used in the following locations Fingers Toes Nose Ear lobes Penis

REGIONAL ANESTHESIA

Regional anesthesia - Definition Rendering a specific area of the body, e.g. foot, arm, lower extremities, insensate to stimulus of surgery or other instrumentation

Regional anesthesia - Uses Provide anesthesia for a surgical procedure Provide analgesia post-operatively or during labor and delivery Diagnosis or therapy for patients with chronic pain syndromes

Regional anesthesia - types Topical Local/Field Intravenous block (“Bier” block) Peripheral (named) nerve, e.g. radial n. Plexus - brachial, lumbar Central neuraxial - epidural, spinal

Topical Anesthesia Application of local anesthetic to mucous membrane - cornea, nasal/oral mucosa Uses : awake oral, nasal intubation, superficial surgical procedure Advantages : technically easy minimal equipment Disadvantages : potential for large doses leading to toxicity

Local/Field Anesthesia Application of local subcutaneously to anesthetize distal nerve endings Uses: Suturing, minor superficial surgery, line placement, more extensive surgery with sedation Advantages: minimal equipment, technically easy, rapid onset Disadvantages: potential for toxicity if large field

IV Block - “Bier” block Injection of local anesthetic intravenously for anesthesia of an extremity Uses any surgical procedure on an extremity Advantages: technically simple, minimal equipment, rapid onset Disadvantages: duration limited by tolerance of tourniquet pain, toxicity

Peripheral nerve block Injecting local anesthetic near the course of a named nerve Uses: Surgical procedures in the distribution of the blocked nerve Advantages: relatively small dose of local anesthetic to cover large area; rapid onset Disadvantages: technical complexity, neuropathy

Plexus Blockade Injection of local anesthetic adjacent to a plexus, e.g cervical, brachial or lumbar plexus Uses : surgical anesthesia or post-operative analgesia in the distribution of the plexus Advantages: large area of anesthesia with relatively large dose of agent Disadvantages: technically complex, potential for toxicity and neuropathy.

Central neuraxial blockade - “Spinal” Injection of local anesthetic into CSF Uses: profound anesthesia of lower abdomen and extremities Advantages: technically easy (LP technique), high success rate, rapid onset Disadvantages: “high spinal”, hypotension due to sympathetic block, post dural puncture headache.

Central Neuraxial Blockade - “epidural” Injection of local anesthetic in to the epidural space at any level of the spinal column Uses: Anesthesia/analgesia of the thorax, abdomen, lower extremities Advantages: Controlled onset of blockade, long duration when catheter is placed, post-operative analgesia. Disadvantages: Technically complex, toxicity, “spinal headache”

TOXICITY OF LOCAL ANESTHETICS Rx of systemic toxicity is primarily supportive: » Stop injection » Administer oxygen » Support ventilation » Tracheal intubation and control ventilation if necessary » Suppress seizure activity (thiopental, midazolam, propofol)