Local and regional anesthesia by dr S Bradulskis

Local and regional anesthesia by dr. S. Bradulskis General surgery department , Kaunas

Local Anesthetic A local anesthetic is an agent that interrupts pain impulses in a specific region of the body without a loss of patient consciousness. Normally, the process is completely reversible--the agent does not produce any residual effect on the nerve fiber.

Chemistry: all local anesthetics are weak bases, classified as tertiary amines.

Characteristics Poorly water soluble weak basic amins (p. Ka 7, 5 -9) Molecular weight: between 220 and 288 Lipophilic aromatic ring + tertiary hydrophilic amin Link: Ester (-COO-) or Amid (-NHC-) chain

Local Anesthetic Classification Aminoesters: Ø Cocaine Ø Procaine Ø Chloroprocaine Ø Tetracaine Aminoamids: Ø Lidocaine Ø Prilocaine Ø Mepivacaine Ø Etidocaine Ø Bupivacaine Ø Ropivacaine Ø Levobupivacaine

Local Anesthetic Metabolism Aminoesters (cocaine, procaine, tetracaine, and chloroprocaine ): ØQuick degradation ØHydrolysis, plasma and liver cholinesterase ØProduces para-aminobenzoic acid (PABA, allergy…. ) Aminoamids (lidocaine, mepivicaine, prilocaine, bupivacaine, and etidocaine ): ØSlower degradation ØLiver microsomal enzymes ØExcretion (metabolites and <5% unchanged drug) via kidneys ØPrilocain (very large doses): Ø- Accumulation of metabolites: risk of methemoglobinemia

Mechanism of Action Ø Local anesthetics work to block nerve conduction by reducing the influx of sodium ions into the nerve cytoplasm. Ø Sodium ions cannot flow into the neuron, thus the potassium ions cannot flow out, thereby inhibiting the depolarization of the nerve. Ø If this process can be inhibited for just a few Nodes of Ranvier along the way, then nerve impulses generated downstream from the blocked nodes cannot propagate to the ganglion.

Effect on Action Ø Effect of protein binding - increased binding increases duration of action Ø Effect of diffusibility - increased diffusibility = decreased time of onset (p. K) Ø Effect of vasodilator activity - greater vasodilator activity = decreased potency and decreased duration of action

Vasoconstrictors Ø Vasoconstrictors decrease the rate of vascular absorption which allows more anesthetic to reach the nerve membrane and improves the depth of anesthesia, it. Ø There is variable response between LA and the location of injection as to whether vasoconstrictors increase duration of action. 1: 200, 000 epinephrine appears to be the best vasoconstrictor.

Effect of lipophilicity ANESTHETIC POTENCY Ø Lipid solubility appears to be the primary determinant of intrinsic anesthetic potency. Chemical compounds which are highly lipophilic tend to penetrate the nerve membrane more easily, such that less molecules are required for conduction blockade resulting in enhanced potency. Ø more lipophilic agents are more potent as local anesthetics

Two forms exist simultaneously: Ø Ionised kation (BH+) Ø Non ionised base (B) Ø Relation between the two forms Ø depends on: Ø p. Ka of the local anesthetic drug Ø Tissue (and solution) p. H Ø Both forms necessary for the action: Ø Neutral base: Ø - Penetrates the membrane Ø of the nerve cell Ø Kation: Active form Ø - Blocks Na-channels (intracellular) The lower the difference between p. Ka and p. H (less basic LA), the more non ionised molecules (base). More non ionised molecules = quicker onset of action

Order of sensory function block Ø 1. pain Ø 2. cold Ø 3. warmth Ø 4. touch Ø 5. deep pressure Ø 6. motor Recovery in reverse order

Susceptibility to block by local anesthetics of types of nerve fibers In general, small nerve fibers are more susceptible than large fibers, however: – the type of fiber – degree of myelination – fiber length and – frequency- dependence are also important in determining susceptibility

A FIBER SIZE AND FUNCTION • α: (dia 12 -20 um; cond vel 70 -120 m/s) largest, afferent to and efferent from muscles and joints. Actions: motor function, proprioception, reflex activity. • β: (dia 5 -12 um; 30 -70 m/s) large as A-alpha, afferent to and efferent from muscles and joints. Actions: motor proprioception, touch, pressure, touch and pressure. • γ: (dia 3 -6 um; 15 -30 m/s) muscle spindle tone. • δ: (dia 2 -5 um; 12 -30 m/s) thinnest, pain and temperature. Signal tissue damage.

B FIBER SIZE AND FUNCTION B fibers: (dia – 2 -5 um) Myelinated preganglionic autonomic. Innervate vascular smooth muscle. Though myelinated, they are more readily blocked by LA than C fibers.

C FIBER SIZE AND FUNCTION C fibers: (dia 0. 4 -1. 2 um) Nonmyelinated, very small nerves. Smallest nerve fibers, slow transmission. Transmit dull pain and temperature, post-ganglionic autonomic. * Both A-d and C fibers transmit pain and are blocked by the same concentration of LA.

TOXICITIES OF LA Ø Essentially all systemic toxic reactions associated with local anesthetics are the result of over-dosage leading to high blood levels of the agent given. Therefore, to avoid a systemic toxic reaction to a local anesthetic, the smallest amount of the most dilute solution that effectively blocks pain should be administered.

Toxicity of LA Ø Signs of toxicity occur on a continuum. From early to late stages of toxicity, these signs are: circum-oral and tongue numbness, lightheadedness, tinnitus, visual disturbances, muscular twitching, convulsions, unconsciousness, coma, respiratory arrest, then cardiovascular collapse.

Toxicity of LA Ø Hypersensitivity. Some patients are hypersensitive (allergic) to some local anesthetics. Although such allergies are very rare, a careful patient history should be taken in an attempt to identify the presence of an allergy. There are two basic types of local anesthetics (the amide type and the ester type). A patient who is allergic to one type may or may not be allergic to the other type.

Toxicity of LA Central Nervous System Toxicities. Ø Local anesthetics, if absorbed systematically in excessive amounts, can cause central nervous system (CNS) excitement or, if absorbed in even higher amounts, can cause CNS depression.

Toxicity of LA to CNS Ø Excitement. Tremors, shivering, and convulsions characterize the CNS excitement. Ø Depression. The CNS depression is characterized by respiratory depression and, if enough drug is absorbed, respiratory arrest.

Toxicity of LA to Cardiovascular system Ø Cardiovascular Toxicities. Local anesthetics if absorbed systematically in excessive amounts can cause depression of the cardiovascular system. Ø Peripheral vascular action arteriolar dilation (except cocaine which is vasoconstrictive Ø Hypotension and a certain type of abnormal heartbeat (atrioventricular block) characterize such depression. These may ultimately result in both cardiac and respiratory arrest.

Systemic toxicity: prevention ØIV access secured before injection of the LA Ø Chose least toxic drug suitable Ø Consider block type and patient specific max. dose ranges ØStart with a „typical dose“ Ø Consider adding a vasoconstrictive adjuvant (epinephrine) ØCareful aspiration during injection Ø Observe clinical reactions: ØTalk to the patient and monitor ECG/blood pressure to realize Øearly symptoms of central-nervous and cardiovascular toxicity Ø Stop injection immediately when early symptoms are realized Ø Consider the time course for development of toxic signs Ø(5 -10 min. after correct injection…. )

Systemic toxicity: treatment Stop injection immediately Treat: ØGive oxygen, (hyperventilate - mask or airway device) ØStop cerebral excitation (Benzodiazepines, Barbiturates, Propofol (Midazolam 2 -5 mg, Thiopental 50 -150 mg, Propofol 50 -100 mg) ØCorrect hypotension and arrhythmias (crystalloids, vasopressors, antiarrhythmic drugs (Ephedrin 5 -10 mg, Epinephrine 10 -100 μg ) ØCardiopulmonary resuscitation for cardiac arrest / VF ØAvoid / treat aggravating factors: Hypoxia and acidosis (respiratory and metabolic)

Influencing factors: patientrelated Age: Old age (> 70 yr): elimination prolonged - 10 -20% dose reduction for continuous applications Newborns (< 4 months): elimination of amid LA prolonged - 15% dose reduction per kg Renal dysfunction: Excretion reduced: - 10 -20% dose reductions relative to degree of dysfuncion Hepatic dysfunction: Low liver blood flow or poor liver function: - Higher blood levels of amid local anesthetics - 10 -50% dose reduction for repeated or continuous applications

Influencing factors: patient-related Body size: In very small adults, the dose for blocks requiring large doses (brachial plexus, IVRA) should be reduced. Pregnancy: ØHormonally increased sensitivity of the CNS to LA: Reduced requirements ØRisk for toxicity ↑: Reduced protein binding of bupivacaine Increased cardiac output, perfusion ↑ and uptake ↑ Anatomic and physiologic changes - 10% dose reduction

Influencing factors: patient-related Infected tissue: ØLow tissue p. H: More ionised kations Less uncharged base available for penetration ØVasodilation: Uptake into circulating blood ↑ Reduced effect of the injected local anesthetic

Influencing factors: not patientrelated Alkalinization (p. H ↑ with sodium bicarbonate): Uncharged base↑, diffusion rate through nerve membrane ↑ - Time to onset ↓ And: Injection is less painful ! (higher p. H) But: Duration of action ↓ Recipe: 9 ml LA (lidocaine, mepivacaine) +1 ml Na. Bic 8. 4% Adjuvant (Epinephrine 1 : 200‘ 000 (5 μg/ml)) Vasoconstriction: Intravascular uptake ↓ - Duration of action 30 -50%↑ only in combination with short acting LA (Lido-, Prilo-, Mepivacaine!) - Toxicity ↓ (all LA) Recipe: 20 ml LA + 0. 1 mg Epinephrine Contraindication for epinephrine: Local anesthesia around end arteries (finger, ear, penis)!

Types of Local Anesthesia • Surface Anesthesia. This type of anesthesia is accomplished by the application of a local anesthetic to skin or mucous membranes. Surface anesthesia is used to relieve itching, burning, and surface pain (for example, as seen in minor sunburns).

• Lidocaine – 5% ointment, 2% gel, 4% solution, 10% aerosol, 100 mg suppository – Onset 3 -5 min • Bensocain – 14 -20% solution, gel, – Onset 30 s

Types of Local Anesthesia • Local Infiltration Local infiltration occurs when the nerve endings in the skin and subcutaneous tissues are blocked by direct contact with a local anesthetic, which is injected into the tissue. Local infiltration is used primarily for surgical procedures involving a small area of tissue (for example, suturing a cut).

Intravenous regional anesthesia. Bier anesthesia Ø How does it work? Ø Injection into a previously exsanguinated and occluded limb Ø Retrograde spread of the distally injected local anesthetic agent Ø Very rapid onset Ø For arm/leg procedures < 1 hour Ø Can be performed with: Prilocaine, Chloroprocaine, Lidocaine (0. 5% solution, 40 -60 ml) Ø Possible complications: LA intoxication when tourniquet is insufficient or released less than 15 - 20 minutes after injection

Types of Local Anesthesia • Peripherial Nerve Block. In this type of anesthesia, a local anesthetic is injected around a nerve that leads to the operative site. Usually more concentrated forms of local anesthetic solutions are used for this type of anesthesia. • Major nerve block - (plexus brachialis) • Minor nerve block - (n. radialis)

Peripheral nerve blocks Choice of agent: Most local anesthetics can be used. Choice depends on intended duration of the block Dose / concentration: Lidocaine, Mepivacaine, Prilocaine (1 % solutions) Bupivacaine (0. 5 % solution), Ropivacaine (0. 75% solution) (10 –) 20 – 40 (– 50) ml (depending on nerve or plexus type) Onset of action and duration: Onset is rapid for Lido/Mepi/Prilocaine and slow for Bupi/Ropi. Time to onset and duration with considerable variations (depending on distance of LA deposit to nerves…) Epinephrine prolongs duration of Lido/Mepi/Prilocaine, but is less effective with Bupivacaine

Brachial plexus block Block possible at different sites: Ø Interscalene: Supraclavicular, Infraclavicular Ø Axillary Chosen site: Depends on planned surgical procedure Injected volume: 30 – 50 ml Time to onset: < 10 min (Lido, Mepi, Prilo) up to 25 min (Bupi, Ropi)

Spinal and epidural anesthesia Main indications: • • • Spinal: Surgery below the umbilicus lower abdomen lower extremities transurethral and vaginal procedures Cesarean section • • • Epidural: Indications as for spinal, +: - Thoracic approach in combination with general anesthesia: abdominal and thoracic surgery Obstetric analgesia Treatment of acute and chronic pain

Spinal and epidural anesthesia Contraindications: • • • Sepsis (Severe) Coagulopathies Shock, severe hypovolemia Infection at/near puncture site Refusal Certain neurologic diseases Severe aortic valve stenosis Communication problems Elevated intracranial pressure Anatomical abnormalities

Spinal and epidural anesthesia: effects Main effects: Anesthesia and analgesia Cardiovascular system: Hypotension (related to: extent of sympathetic block, volemia) Bradycardia (blocked sympathetic cardioaccelerator fibers; Young males: more frequent) Both effects more pronounced with spinal than with epidural anesth. Respiratory system: Reduced active exhalation with high block level: - Caution in patients with severe COPD!

Spinal and epidural anesthesia: effects • • • Gastrointestinal and urogenital: Unopposed parasympathetic activity: Nausea (associated with high block level) Increased secretions, relaxed sphincters, bowel constriction Long lasting block of sacral parasympathetic nerves: Postoperative urinary retention possible Endocrine-metabolic: Less perioperative stress-response: Reduction of: protein catabolism, hyperglycemia, sodium and water retention, fever, tachycardia, increased minute ventilation Coagulation: Reduced hypercoagulability, reduced thromboembolic events

• Spinal Anesthesia. In spinal anesthesia, the local anesthetic is injected into the subarachnoid space of the spinal cord

Spinal anesthesia • Only use drugs without preservatives! • Commonly used: 0. 5% Bupivacaine (long action) • hyperbaric (with 8% glucose) or plain (isobaric) solution • No hyperbaric (=heavy) lidocaine (transient neural symptoms)! • Rapid onset (injection close to nerve roots)

Epidural Anesthesia. This type of anesthesia is accomplished by injecting a local anesthetic into the epidural space • Lido-, Mepiva-, Prilo-, Bupiva, Ropivacaine • Onset 5 -15 min (Lido/Mepi/Prilo) to 20 -30 min (Bupi/Ropi) • Anesthesia: • high concentration: 2% Lido/0. 5% (L-)Bupi/0. 75% Ropi • Analgesia postoperative without motor deficit: • 0. 125 -0. 25% (L-)Bupi/0. 2% Ropi

Postoperative Analgesia Local anesthetics for postoperative analgesia: Thoracic Epidural analgesia Continuous peripheral nerve blocks (Shoulder, Arm, Leg) Continuous wound infiltration (Shoulder, Tram-Flap, …. )

Postoperative epidural analgesia Advantages compared with systemic opioid-based analgesia: Decreased postoperative pain Better analgesic effect Reduced opioid related side-effects (Nausea/Vomiting, Pruritus, Sedation) Also suitable for some outpatients (elastomere pumps) Less sedation, less postoperative fatigue Higher „Health related quality of life“ Earlier mobilization Better respiratory function, better exercise capacity, better bowel function, earlier oral nutrition Earlier ready for discharge (not done, other factors…. ) No difference: incidence of postoperative surgical complications But: Method-specific side effects (similar to regional anesthesia