Local anesthetics

Local anesthetics are drugs of selective action, purposefully providing a reversible interruption, first of all, of pain impulses in the conductors of the peripheral nervous system.

For the first time on the opportunity to selectively change pain sensitivity and achieve local anesthesia of tissues drew attention VK. Anrep (1878), who described the local anesthetic effect of cocaine isolated almost 20 years before by the German chemist Niemann (1860) from the leaves of Erythroxylum coca. Soon, Carl Koller (K. Roller, 1984) successfully used a solution of cocaine to anesthetize the manipulation of the cornea of the eye. The next two decades have become an impressive demonstration of the vast possibilities of clinical use of cocaine for local anesthesia of various areas. These kinds of perspectives were constantly fueled by the unrelenting interest of clinicians in seeking an alternative to the early realized risks of mask anesthesia.

The appearance of procaine (Einhorn, 1904), and later also the synthesis of other, less toxic drugs with local anesthetic activity (tetracaine - 1934, lidocaine - 1946, bupivacaine - 1964, ropivakin -1994, etc.) along with development and improvement of a variety of technical techniques that ensure the achievement of a blockade of painful conductors for different regions of the body, this approach in the evolution of local anesthesia was justified at this stage of anesthesia development.

Currently, local anesthesia represents a separate area of anesthesiology, encompassing both a variety of techniques for administering local anesthetics and operational pathophysiology, for which the pharmacological effects of these drugs are responsible, and is used as the primary or special component of anesthesia. From the positions of application of local anesthetic effects, it is customary to distinguish:

• application anesthesia;
• infiltration anesthesia;
• in / in the regional under the harness according to A. Biru;
• conductor blockade of peripheral nerves;
• conductive blockade of the nerve plexus;
• epidural anesthesia;
• subarachnoidal anesthesia.

The availability and accessibility of highly effective, but differing in the spectrum of the main action of local anesthetics made the choice of drugs for local anesthesia really an independent problem. This variety of clinical manifestations of the main pharmacological action is fairly associated with both histomorphological and physiological features of nerve structures and with the physico-chemical properties of the drug itself, which determines the peculiarity of the pharmacodynamics and pharmacokinetics of each of the drugs and various variants of local anesthesia. Therefore, the choice of a local anesthetic should be considered as the first step towards achieving rational and safe local anesthesia.

Chemical compounds with locally anesthetic activity have certain common structural features. Lufgren first noted that almost all local anesthetics consist of a hydrophilic and hydrophobic (lipophilic) constituents separated by an intermediate chain. The hydrophilic group is basically secondary or tertiary amines, and the hydrophobic group is usually an aromatic residue. On the differences in the structure of the compound with the aromatic group, a classification of local anesthetics is constructed. Local anesthetics with an ether compound between the aromatic moiety and the intermediate chain are known as amino esters. Examples of local anesthetics in this group are cocaine, procaine and tetracaine. Local anesthetics with an amide compound between an aromatic group and an intermediate chain are known as aminoamides and are represented by such anesthetics as lidocaine, trimecaine, bupivacaine, and other known drugs. The type of connection with the aromatic group determines the metabolic pathways of local anesthetics; ethereal compounds are readily hydrolyzed in plasma by pseudocholinesterase, while amide local anesthetics are metabolized more slowly by liver enzymes.

[1], [2], [3], [4], [5]

Local anesthetics: a place in therapy

The ability of local anesthetics to cause a total conductor block and regional anesthesia or to selectively turn off sympathetic or sensory innervation is now widely used in anesthetic practice both to provide a variety of surgical interventions, and for therapeutic and diagnostic purposes. At the same time, the conductive blockade is realized either as the main one or as a special component of the anesthesia aid.

It is expedient to distinguish variants of peripheral and central, or segmental, anesthesia. The term "anesthesia" implies the achievement of a blockade of all kinds of sensitivity, while analgesia characterizes the exclusion of primarily sensory sensitivity. A similar terminological burden is borne by the concept of a block, whereas the term "blockade" should be used to refer to the technique of some, in particular, conductive, variants of local anesthesia. In the domestic literature the term "regional anesthesia" covers only the technique of conductive blockades. However, it is fair, as emphasized in all modern guidelines, for all variants of local anesthesia. The term "prolonged conductive anesthesia" implies the use of the technique of catheterization of the paraneural structures in order to maintain the block by repeated injections or infusion of solutions of local anesthetics both in the intra- and postoperative period:

• Application anesthesia is achieved by applying (spraying) highly effective local anesthetics (for example, 2-10% lidocaine solution) to the skin or mucous membranes (for example, Bonica intratracheal anesthesia). To this variant of anesthesia is the introduction of a local anesthetic into cavities coated with a serous membrane, rich in a receptor apparatus (for example, intrapleural anesthesia);
• infiltration anesthesia involves the sequential injection of a local anesthetic solution into soft tissues in the area of the proposed operation. The most effective variant of such anesthesia is considered to be anesthesia using the creeping infiltrate method according to A.V. Vishnevsky;
• conductor anesthesia of peripheral nerves includes accurate verification of anatomical structures for the purpose of creating a compact depot of local anesthetic. The greatest practical importance is the blockade of large nerve trunks of the limbs;
• IV regional anesthesia is used for operations up to 100 min on the upper and lower extremities below the peripheral turnstile. Local anesthetics (0.5% solutions of lidocaine or prilocaine without epinephrine) are injected into the peripheral vein after applying a double-lumen pneumatic turnstile in a volume of up to 50 ml for the upper limb or up to 100 ml for the lower extremity. This anesthesia is preferable for operations on soft tissues. Operations on bones and nerves in these conditions can be painful. A variant of intravenous anesthesia is intraosseous anesthesia with a 0.5% lidocaine solution at a dose of up to 6 mg / kg, when local anesthetics are injected into tubular bones in places where there is a thin cortical layer;
• The conductor blockade of the nerve plexuses is based on the creation of a compact depot of a local anesthetic within the anatomical case containing nerve trunks. Given the anatomical features of the structure of various nerve plexuses, several levels are distinguished for achieving an effective blockade (eg, axillary, subclavian, supraclavicular and lacrimal access to the brachial plexus);
• epidural anesthesia is achieved by the introduction of solutions of anesthetics into the epidural space with the development of blockade of the spinal roots or spinal nerves passing through it;
• spinal (subarachnoid) anesthesia occurs as a result of the injection of a local anesthetic solution into the cerebrospinal fluid of the spinal subarachnoid space;
• combined spinal epidural anesthesia is a combination of spinal and epidural blockages when the needle for the puncture of the epidural space (the Tuohi type needle) serves as a conduit for inserting a thin (26G) needle for the purpose of subarachnoid injection of a local anesthetic and subsequent catheterization of the epidural space.

The principal differences in the indications for the use of a local anesthetic with respect to a specific technique for its administration is the correspondence of the pharmacological properties of drugs to the nature of surgical intervention. Short-term operations, often performed on an outpatient basis, require the use of local anesthetics with a short duration of action, such as novocaine and lidocaine. This choice of drugs provides a short period of recovery of the patient and shortens the period of his stay in the medical institution. Conversely, in operations that last more than 2 hours, the use of bupivacaine and ropivacaine is indicated. The urgency of the clinical situation makes it necessary to choose not only local anesthetics with a short latent period, but also a technique that has such an advantage, for example, subarachnoid anesthesia with a 0.5% bupivacaine solution or 0.5% tetracaine solution to perform an emergency cesarean section.

In addition, the peculiarities of obstetrical practice make an anesthesiologist choose a local anesthetic with minimal systemic toxicity. Recently, such drugs have become ropivacaine for pain relief and vaginal delivery and caesarean section.

Achievement of special effects of regional blockades (regional sympathetic block, postoperative analgesia, treatment of chronic pain) is provided by using low concentrations of solutions of local anesthetics. The most popular drugs for this purpose are 0,125-0,25% solutions of bupivacaine and 0.2% solution of ropivacaine.

Mechanism of action and pharmacological effects

The object of interest of local anesthetics is the peripheral nervous system. It includes rootlets, branches and trunks of both cranial and spinal nerves, as well as components of the autonomic nervous system. The peripheral and central nervous system can be divided into crude anatomical and histological components in accordance with two stages of development of local anesthesia. The gross anatomical structure of nervous formation determines the latent period of the drug blockade, which is applied at this location. In contrast, the histological structure, in addition to the concomitant neurophysiological factors (pain, inflammation) that affects the effect of drugs, determines the penetrating ability of drugs through the nerve fiber shells before its function is interrupted.

Nerve fibers are functional units of the peripheral nerve. This term refers exclusively to an axon originating from a centrally located neuron, but more often it is used as a broader definition, referring in addition to the neuron and the Schwann cell membrane that surrounds it. This shell provides structural and support functions, but its most significant function is to participate in the transfer of momentum.

There are two types of nerve fiber device. In the first type, protrusion from one Schwannian cell surrounds several axons, which are described as demyelin. In compounds, Schwann cells, which have a maximum length of 500 microns, simply overlap each successive one. Another type of device consists of the protrusion of each Schwannian cell, which repeatedly wraps one axon. Such an axon is surrounded by a "tube" formed by multiple double layers of the phospholipid cell membrane, the myelin sheath. Each Schwannian cell extends to 1 mm or more, and at the junctions (Ranvier intercepts) myelin is absent. At the same time, significant spacing between the processes of individual cells is overlapped by protrusions, so that the axonal membranes have an additional envelope. Axoplasm contains common organelles, such as mitochondria and vesicles, which are necessary for normal cellular metabolism. There is a possibility that some chemical "transmitters" pass into axoplasm.

Differences in the histomorphological structure of the fibers that make up the nerve, make it possible to achieve a differentiated blockade of fibers bearing a specific functional load. This becomes possible when the nerve is exposed to various local anesthetics in different concentrations, which is often necessary in the clinical practice of regional blockades.

The most important structure of transmission of nerve impulses is the axonal membrane. Its basic structure is a double plate of phospholipids, oriented so that the polar hydrophilic phosphate groups are in contact with the interstitial and intracellular fluid. The hydrophobic lipid groups are directed, on the contrary, to the center of the membrane. Large molecules of protein are included in the membrane. Some of them carry a structural function, others are active and function as enzymes, receptors for hormones and drugs or as channels for the movement of ions from the cell and into it.

To realize the effects of local anesthetics, these protein ion channels are most important. Everyone has a time through which ions move. There are several different types of filters that make the channel specific to a certain ion. This specificity can be based on the pore diameter, or on the electrostatic properties of the channel, or both. Many channels still have gates that regulate the movement of ions through them. This is due to the sensory mechanism, which causes structural changes in the protein, accompanied by the opening or closing of the gate. Local anesthetics cause a decrease in the permeability of the cell membrane to sodium ions, so that although the resting potential and the threshold potential are preserved, there is a noticeable depression of the membrane depolarization rate, which makes it insufficient to reach the threshold potential. Therefore, the spread of the action potential does not occur, the conductivity block develops.

It was found that the increase in sodium permeability is associated with the depolarization of the cell membrane and is provided by opening a gate or pore (sodium channel) in it. The exit of sodium from the cell through the pores is prevented by the excess of calcium ions. The opening of the sodium channel is explained by the movement of calcium into the extracellular fluid during depolarization. In a state of rest, calcium ions contribute to the fact that the channel remains closed. These hypotheses are based on the hypothesis that local anesthetics compete with calcium ions for placement in the sodium channel, i.e. They compete with calcium for a receptor that controls the permeability of the membrane to sodium ions.

The exact mechanism of action of a local anesthetic is to this day the subject of discussion. Three main mechanisms for blocking the nerve conduction caused by these drugs are discussed:

• receptor theory, according to which local anesthetics interact with the receptors of the sodium channels of the nerve membrane, blocking the conductivity along the nerve;
• the theory of membrane expansion allows that local anesthetics cause expansion of the nerve membrane, squeeze sodium channels, thereby blocking nerve conduction;
• the theory of surface charge is based on the fact that the lipophilic portion of the local anesthetic binds to the hydrophilic link of the end of the nerve membrane. This ensures that the positive charge is exceeded, so that the transmembrane potential rises. The approaching impulse can reduce the potential to threshold levels, and a conduction block appears.

Many biotoxins (for example, tetrodotoxin, saxitoxin), phenothiazines, beta-blockers and some opioids are able to block sodium channels in their in vitro application. But only local anesthetics are used in clinical practice for blockade of nerve conduction, since they are able to penetrate the nerve membrane and are relatively free from local and systemic toxicity. The basis of the mechanism of action of these drugs is their chemical behavior in solution. All clinically used local anesthetics have common structural elements: an aromatic ring and an amine group connected by an intermediate chain. In addition to the blockade of pain impulses, local anesthetics have clinically significant concomitant effects on the CNS, CCC, and neuromuscular transmission.

Influence on the central nervous system

Local anesthetics easily penetrate the BBB, causing CNS stimulation, and with excess doses - its depression. The severity of CNS response effects correlates with the concentration of drugs in the blood. At the so-called therapeutic concentrations of anesthetic in the plasma, minimal effects are observed. Small symptoms of toxicity are manifested in the form of numbness of the tongue and skin around the mouth, which can be accompanied by ringing in the ears, nystagmus and dizziness. The continued increase in the concentration of anesthetic in plasma causes CNS excitation in the form of anxiety and tremor. These symptoms indicate the proximity of the concentration of drugs to the toxic level, which is manifested by convulsions, coma and stopping blood circulation and breathing.

Influence on the cardiovascular system

Local anesthetics cause peripheral arteriolar dilatation and myocardial depression. The concentration in the plasma of lidocaine, ranging from 2 to 5 μg / ml, causes weak peripheral vasodilation, the absence or minimal changes in contractility, diastolic volume and CB. Lidocaine in a concentration of 5 to 10 μg / ml progressively worsens myocardial contractility, increases diastolic volume and reduces CB. At concentrations above 10 μg / ml, OPSS depression and a significant decrease in myocardial contractility occur, leading to profound hypotension. Cardiovascular effects of local anesthetics usually do not occur with most regional anesthesia unless a random intravascular injection occurs when a high concentration in the blood is created. This situation is typical for epidural administration of anesthetics as a result of an absolute or relative overdose.

Some local anesthetics have an antiarrhythmic effect on the heart. Procaine increases the refractory period, raises the threshold of excitability and increases the time spent. Although procaine is not used as an antiarrhythmic drug, procainamide remains popular in the treatment of cardiac arrhythmias.

Influence on neuromuscular conduction

Local anesthetics can affect neuromuscular conduction and, in certain situations, potentiate the effects of depolarizing and nondepolarizing muscle relaxants. In addition, there are isolated reports linking the development of malignant hyperthermia with the use of bupivacaine.

Pharmacokinetics

Physicochemical characteristics

Structural changes in the molecule significantly affect the physico-chemical properties of drugs that control the power and toxicity of the local anesthetic. Fat solubility is an important determinant of anesthetic power. Changes in either the aromatic or amine portion of the local anesthetic can alter fat solubility and therefore anesthetic power. In addition, elongation of the intermediate link leads to an increase in anesthetic power until it reaches a critical length, after which the power is usually reduced. Increasing the degree of binding to proteins leads to an increase in the duration of local anesthetic activity. Thus, the addition of the butyl group to the aromatic residue of the etheric local anesthetic of procaine increases the fat solubility and the ability to bind to the protein. In this way, tetracaine was obtained, which has a high activity and a long duration of action.

Thus, the severity of the basic pharmacological action of local anesthetics depends on their fat solubility, the ability to bind to plasma proteins, as well as pKa.

Fat solubility

Highly soluble drugs easily penetrate the cell membrane. In general, the most fat-soluble local anesthetics are more potent and have a longer duration of action.

[6], [7], [8]

Binding to proteins

The increased duration of the anesthetic effect correlates with the high ability to linger in the plasma. Although binding to the protein reduces the amount of free drug that is capable of diffusion, it secures the deposition of drugs to preserve local anesthesia. In addition, the binding of a greater mass of active drugs to plasma proteins reduces the likelihood of a systemic toxicity of the local anesthetic.

[9], [10], [11], [12],

Dissociation constant

The degree of ionization plays a large role in the distribution of drugs and largely determines the severity of its main pharmacological effect, only non-ionized forms of it easily pass through the cell membranes. The degree of ionization of a substance depends on the nature of this substance (acid or base), pKa and pH of the medium in which it is located. PKa LS is the pH at which 50% of the drug is in ionized form. A weak base is more ionized in an acidic solution, so lowering the pH will increase the ionization of the base. Local anesthetics are weak bases with pKa values of 7.6 to 8.9. Local anesthetics with a pKa value close to physiological pH (7.4) are represented in solution by a greater concentration of non-ionized form of molecules (which diffuses more easily through nerve boxes and membranes to their site of action) than local anesthetics with higher pKa. LS with high pKa will dissociate more at physiological pH, and therefore there is less non-ionized drug capable of penetrating the nerve case and membrane. That is why local anesthetics with pKa values close to physiological pH values tend to start more quickly (lidocaine - 7.8, mepivacaine - 7.7).

In light of the foregoing, the reasons for the low effectiveness of amino-ethers, procaine and tetracaine, become more understandable. As can be seen in Table 6.2, procaine is characterized by low fat solubility, a weak ability to bind to proteins and a very high pKa value. On the other hand, tetracaine at first glance, at least in two respects, is approaching the ideal local anesthetic. This is confirmed by the fact that it is well known to clinicians that it is highly potent. One could reconcile with the long latent period of tetracaine, which is determined by high pKa, but insufficiently high binding of drugs to proteins is responsible for a high concentration of active substance in the blood. If procaine is just a mild local anesthetic, tetracaine should be considered an extremely toxic local anesthetic. Because of this, today it is permissible to use tetracaine only for application and subarachnoid anesthesia.

On the contrary, modern local anesthetics, available today aminoamides (lidocaine, ultracaine and bupivacaine), favorably differ from procaine and tetracaine in their physicochemical properties, which predetermines their high efficiency and sufficient safety. The rational combination of physical and chemical properties, inherent in each of these drugs, predetermines a high range of clinical opportunities in their use.

The emergence of highly effective local anesthetics (articaine and ropivacaine) broadens the choice of local anesthetic for various conductive blockades. Artikain - a new local anesthetic has unusual physical and chemical properties: pKa = 8.1; fat solubility - 17; binding with proteins - 94%. This explains its minimal toxicity and features of clinical pharmacology - a short latent period and a relatively long duration of action.

Knowledge of the pharmacokinetic laws of the behavior of local anesthetics in the body is of vital importance in carrying out local anesthesia (Table 6.3), tk. The systemic toxicity and severity of the therapeutic effect of these drugs depend on the balance between the processes of their absorption and systemic distribution. From the injection site, the local anesthetic penetrates the blood through the walls of the blood vessels and enters the systemic circulation. The active blood supply of the CNS and CCC, as well as the high lipid solubility of local anesthetics predispose to rapid distribution and growth of concentrations to potentially toxic levels in these systems. This is counteracted by ionization processes (cations do not cross the membrane), binding to the protein (bound LS is also not capable of crossing the membrane), biotransformation and renal excretion. Further re-distribution of drugs to other organs and tissues occurs depending on regional blood flow, concentration gradients and solubility coefficients.

[13], [14], [15], [16]

Absorption

The pharmacokinetics of local anesthetics can be divided into two main processes - the absorption kinetics (absorption) and the kinetics of systemic distribution and elimination (elimination).

Most pharmacokinetic studies of local anesthetics in humans included measuring their concentrations in the blood at different times after drug administration. The concentration of drugs in the plasma depends on the absorption from the site of introduction, interstitial distribution and elimination (metabolism and excretion). Factors determining the severity of systemic absorption include the physico-chemical properties of the local anesthetic, the dose, the route of administration, the addition of the vasoconstrictor to the solution, the vasoactive properties of the local anesthetic, and the pathophysiological changes caused by the underlying comorbidities.

So, systemic absorption after epidural injection can be represented as a two-phase process - the formation of a local anesthetic depot and proper absorption. For example, absorption from the epidural space of a long-acting, well-fat-soluble, with a high ability to bind to anesthetic proteins will occur more slowly. This is probably due to a greater delay in drugs in the fat and other tissues of the epidural space. It is clear that the vasoconstrictive effect of epinephrine will have an insignificant effect on the absorption and duration of action of a long-acting drug. At the same time, the slow absorption of long-acting drugs causes less systemic toxicity.

The injection site also affects the systemic absorption of drugs, because blood flow and the presence of tissue proteins capable of binding local anesthetics represent important elements that determine the activity of drug absorption from the site of administration. The highest concentrations in the blood were found after the intercostal block, and they decreased in the following order: caudal blockade, epidural block, blockade of the brachial plexus, blockade of the femoral and sciatic nerves, and subcutaneous infiltration with a local anesthetic solution.

[17], [18],

Distribution and deduction

After the local anesthetics are absorbed from the injection site and into the systemic circulation, local anesthetics first rush out of the blood into the interstitial and intracellular fluids, and then are eliminated mainly by metabolism and in small amounts through renal excretion.

The distribution of drugs is affected by its physical and chemical properties, such as fat solubility, binding to the plasma protein and the degree of ionization, as well as physiological conditions (regional blood flow). Long-acting amide local anesthetics are more closely bound by the plasma protein than the short acting amide and ether local anesthetics. In addition, these local anesthetics also bind to erythrocytes, and the ratio of blood / plasma concentrations is inversely proportional to plasma binding. The main binding protein for most basic amide local anesthetics is a-glycoproteinic acid, and the decrease in mepivacaine binding in neonates is explained, in particular, by the small amount of their a1-glycoproteinic acid.

Anesthetics of the amide type are metabolized mainly in the liver, so their clearance decreases in such disease states as heart failure, cirrhosis, when the blood flow of the liver is reduced.

Anesthetics of the etheric type disintegrate both in plasma and in the liver, undergoing rapid hydrolysis by plasma cholinesterase. The metabolic rate varies significantly for different drugs. Chlorprocarin has the highest hydrolysis rate (4.7 μmol / ml h), procaine 1.1 μmol / ml h and tetracaine 0.3 μmol / ml h. This explains their difference in toxicity; Chlorprokain - the least toxic LAN of the ester group, and tetracaine is the most toxic anesthetic. Excretion of local anesthetics is carried out by the kidneys and liver mainly in the form of metabolites and to a lesser degree in the unchanged state.

[19], [20], [21], [22]

Contraindications

Contraindications for the use of local anesthetics are:

• references to allergic reactions to local anesthetics;
• The presence of infection in the area of their intended introduction.

Relative contraindications include all conditions associated with hypoproteinemia, anemia, metabolic acidosis and hypercapnia.

[23], [24], [25], [26]

Tolerance and side effects

Allergic reactions

Allergy to local anesthetics is rare, and can manifest as local edema, urticaria, bronchospasm and anaphylaxis. Dermatitis can occur after dermal applications or as contact dermatitis in dentistry. Derivatives of ethereal anesthetics - derivatives of para-aminobenzoic acid cause most of the hypersensitivity reactions, and hypersensitivity to amide local anesthetics is extremely rare, although some observations of hypersensitivity to lidocaine have been described.

[27], [28], [29], [30]

Local Toxicity

An example of local toxicity is the development of the "ponytail" syndrome in the practice of subarachnoid anesthesia with lidocaine. The main cause of the damaging effect of this widely used drug are weak diffusion barriers lying between the anesthetic and the subarachnoid nervous structures. The use of more concentrated solutions than is recommended for each of the techniques can lead to the development of a neurological deficit, which is a manifestation of the local toxicity of local anesthetics in relation to the corresponding variants of local anesthesia.

Systemic Toxicity

Excess absorption of local anesthetics into the blood is the cause of systemic toxic reactions. Most often this is a random intravascular injection and / or absolute or relative, due to the presence of concomitant pathological changes, drug overdose. The severity of manifestations of toxicity of local anesthetics closely correlates with the concentration of drugs in the plasma of arterial blood. The factors that determine the concentration of drugs in the blood plasma and, consequently, the toxicity of the anesthetic include the injection site and the injection rate, the concentration of the solution administered and the total dose of the drug, the use of the vasoconstrictor, the rate of redistribution in various tissues, the degree of ionization, the degree of binding to the plasma protein, and tissues, as well as the rate of metabolism and excretion.

Clinical picture of toxic reactions

The toxic effects of local anesthetics are manifested by changes in the cardiovascular system (CCC) and CNS. There are 4 phases of the manifestations of a toxic reaction to a local anesthetic from the side of both the central nervous system and the CCC.

Particularly sensitive to the toxic effects of bupivacaine on CCC are pregnant. SSS is more resistant to the toxic effects of local anesthetics than the central nervous system, but powerful local anesthetics, in particular bupivacaine, can cause severe disruption of its function. Cases of development of ventricular arrhythmias are described.

[31], [32], [33], [34], [35], [36],

Treatment of toxic reaction

Early, timely diagnosis of toxic reactions and the immediate onset of treatment are the key to patient safety in regional anesthesia. Obligatory availability and availability for use of all equipment and medicines for the treatment of toxic reactions. There are two basic rules:

• always use oxygen, and if there is a need, then artificial ventilation through the mask;
• to cramp seizures if they last more than 15-20 sec, IV injection of 100-150 mg of thiopental or 5-20 mg of diazepam.

Some specialists prefer to administer 50-100 mg of suxamethonium, which quickly stops convulsions, but requires intubation of the trachea and ventilation. Manifestations of a toxic reaction may disappear as quickly as they appeared, but at this time a decision should be made: either postpone the operation and repeat the conductive blockade using a different technique (eg spinal anesthesia instead of epidural), or proceed to general anesthesia.

If there are signs of hypotension or myocardial depression, it is necessary to use a vasopressor with alpha and beta-adrenergic activity, in particular ephedrine at a dose of 15-30 mg IV. It should be remembered that the use of solutions of local anesthetics containing epinephrine completely excludes the inhalation of ftorotan during anesthesia, as this results in sensitization of the myocardium to catecholamines followed by the development of severe arrhythmia.

Heart failure caused by an overdose of local anesthetics requires prolonged and intensive resuscitation, often unsuccessful. This dictates the need to observe precautionary measures and not to neglect all measures of prevention of intoxication. To begin intensive therapy follows at the earliest stages of its development.

Interaction

Against the backdrop of local anesthesia conducted by lidocaine, there is always the danger of an absolute or relative overdose of drugs in the case of attempts to use lidocaine to treat ventricular extrasystoles, which can lead to the development of systemic toxicity.

A reassessment of the need to abolish beta-blockers dictates the need for careful use of local anesthetics for regional blockades because of the dangers of developing a threatening bradycardia that can masquerade as the effects of a regional sympathetic block. Similarly, the risk of bradycardia and hypotension is present when using drugs with alpha-adrenolytic activity (droperidol) in conditions of regional blockades.

Vasoconstrictors

The use of vasopressors with regional blockades has at least two distinct aspects. It is generally recognized that vasoconstrictors can enhance effects and increase the safety of regional blockade by slowing the absorption of local anesthetics in the injection zone. This applies to both central (segmental) and peripheral blockages of nerve wires. Recently, great importance is attached to the mechanism of direct adrenomimetic action of epinephrine on the adrenergic antinociceptive system of the gelatinous substance of the spinal cord. Due to this direct action, the basic pharmacological effect of the local anesthetic is potentiated. This mechanism is more important in spinal than in epidural anesthesia. At the same time, due to the peculiarities of the blood supply to the spinal cord, one should not forget about the danger of ischemic injury with serious neurological consequences as a result of the local effect of excessive concentrations of epinephrine on the arteries of the spinal cord. A reasonable solution in this situation is either the use of formal solutions containing a fixed dose of epinephrine (5 μg / ml), or a refusal to add it to a local anesthetic ex tempore. The last conclusion is determined by the fact that in clinical practice it is often permissible to dose epinephrine in droplets, which is mentioned in domestic articles, manuals, and sometimes in annotations to a local anesthetic. The safe practice of preparing such a solution involves the dilution of epinephrine to a concentration of not less than 1: 200,000, which corresponds to the addition of 0.1 ml of a 0.1% solution of epinephrine to 20 ml of a local anesthetic solution. Apparently, the use of this kind of combination has the right at one-time technique of epidural blockade, whereas with prolonged infusion of anesthetic, a technique widely popular in obstetrics, the likelihood of neurological complications increases many times. When performing peripheral blockades, it is permissible, in particular, in dental practice, the use of epinephrine and in a dilution of 1: 100,000.

Local anesthetics of the ester group hydrolyze, forming para-aminobenzoic acid, which is an antagonist of the pharmacological action of sulfonamides. Aminoethers can prolong the effect of suxamethonium, t. They are metabolized by the same enzyme. Anticholinesterase drugs increase the toxicity of conventional doses of procaine, inhibiting its hydrolysis. Novocaine metabolism is also reduced in patients with congenital pathology of plasma cholinesterase.

Caveats

Toxic reactions can be avoided in most cases subject to a number of rules:

• Do not start anesthesia without oxygen inhalation with a mask;
• Always use only recommended doses;
• Before injection of a local anesthetic through a needle or catheter, always perform aspirating tests;
• use a test dose of a solution containing epinephrine. If the needle or catheter is located in the lumen of the vein, the test dose will cause a rapid increase in heart rate in 30-45 seconds after the injection. Tachycardia quickly goes away, but in this situation, constant ECG monitoring is necessary;
• if there is a need to use large volumes of drugs or inject it intravenously (eg, intravenous regional anesthesia), use drugs with minimal toxicity and ensure a slow distribution of drugs in the body;
• always inject slowly (no faster than 10 ml / min) and maintain verbal contact with the patient, who can immediately report minimal manifestations of the toxic reaction.

[37], [38], [39]