BG61992B1 - Device for the antagonization of the toxic effect of lidocaine on the central and the vegitative nervous system - Google Patents

Abstract

According to this invention the antagonization of the toxiceffect of Lidocaine is attained by the application ofgalantaminechidrobromine (the Nivalin preparation) as an antidoteof Lidocaine. The method for the neutralization of the toxiceffect of Lidocaine on the central and the vegitative nervoussystem consists in fractioned subcutaneous or intravenousapplication of Nivalin at initial dose of 2.5 mg until theachievement of optical therapeutical effect - completeantagonization of the toxic effect of Licodaine. The use ofNivalin for controlling the toxic effect of Lidocaine removes anynecessity for the application of other preparations having adverseeffect on the patient in this state, and for endotrachealintubation and equipment ventilation. The preparation has an easyand convenient scheme of application with the potentials ofcontrolling the critical situation without having any need forspecial complex and expensive equipment and/or specially trainedstaff for resuscitation operations.

Description

Technical field

The invention relates to the field of medicine, in particular to the administration of lidocaine, as a topical anesthetic and as an antiarrhythmic agent, with undesirable side effects classified as "systemic toxic effects". The invention also relates to the field of manufacture and use of medicines.

BACKGROUND OF THE INVENTION

Lidocaine is a widespread drug in clinical practice because of its good therapeutic effect in controlling the manifestations of ventricular excitability and as a local anesthetic.

Adverse reactions with different manifestations and severity occur according to different authors / 1, 2, 3, 4 / with different frequency. For some of the authors / 1,3 / the response of the organism as hypersensitivity to local anesthetics is the cause of no more than 1% of the observed incidents. The remaining 99% were acute intoxication as a result of rapid absorption into the bloodstream or intravenous injection. According to other authors / 4 / cases of seizures and cardiac collapse associated with local and in particular regional anesthesia are from 1 to 4/1000.

The side effects after lidocaine administration occur after 1 to 30 times depending on the route of administration. The clinical picture is presented mainly by changes in the central nervous system and the cardiovascular system - tremor of the transversely muscled muscles, choreiform movements, convulsions, mental arousal, diplopia. Post-initial breathing is gradually suppressed by apnea and respiratory failure. The heart rate slows down. With regional blockage, blood pressure decreases. In advanced intoxication, CNS depression, breathing, vasomotor regulation, bradycardia, increased ventricular extrasystole, A - V block, etc. develop. The final stage of intoxication is demonstrated by spore, coma, cyanosis, apnea and circulatory arrest (1, 2, 3, 4, 5).

To neutralize the toxic effect of lidocaine, various agents and methods have been applied (1, 2, 3, 5).

Intravenous fast acting barbiturates or benzodiazepines are administered. Some authors have doubts about their use due to the synergism of their action with that of the local anesthetic. The result is a deepening of respiratory depression and circulatory collapse / 2 /.

(2) Application of muscle relaxants, endotracheal intubation and apparatus ventilation is recommended. Oxygen delivery is considered a mandatory action because of the presumed "tissue hypoxia" as a generator of systemic toxic effects.

The problems associated with the toxic effects of lidocaine and their elimination cannot be resolved with the approach taken so far. First of all, what is known in the clinical picture literature is descriptive. The mechanism of toxic action is unknown. It is well established that the action on the human body is accomplished by influencing the potentially dependent sodium channels in the transmission of nerve impulses. This mechanism of action could not explain the development and diversity in the clinical picture of the systemic toxicity of the local anesthetic.

No systematization of the manifestations of intoxication and grading of its severity has been done. The established scheme of influence is rather empirical. Remedies and methods, especially in critical situations, aim to maintain adequate ventilation and satisfactory hemodynamics. The actions are aimed at maintaining the vital functions of the body with universal means until the toxic effect of lidocaine is exhausted.

SUMMARY OF THE INVENTION

Problems related to neutralizing the toxic effect of lidocaine are solved according to the invention by administering galanthamine hydrobromide (preparation nivalin) as an antidote to lidocaine. The method of neutralizing the toxic effect of lidocaine on the central nervous system and the autonomic nervous system consists in fractional subcutaneous or intravenous administration of nivalin at an initial dose of 2.5 mg to achieve the optimal therapeutic effect - complete antagonization of the toxic effect of lidocaine.

The preparation nivalin is a known pharmacopoeial preparation (6), with wide application in neurology, ophthalmology, gastroenterology, resuscitation, cardiology, physiotherapy, where stimulation and potentiation of synaptic acylcholine mediation is required.

The use of nivalin in controlling the toxic effects of lidocaine is of great value in daily medical practice:

- the use of the recommended treatment regimen with barbituric derivatives, benzodiazepines, muscle relaxants, as well as the use of endotracheal intubation and apparatus ventilation is eliminated;

- there is an easy and convenient scheme of administration - a gradually increasing dose of 2.5 lbs until satisfactory results are achieved;

- the ability to cope with a critical situation without the need for special equipment from complex and expensive equipment and / or specially trained resuscitation resuscitation personnel.

Embodiments of the invention

1. Surgery with epidural administration of 150 mg of lidocaine develops 15 πιίη then a typical clinical picture of acute intoxication: muscular tremor that has turned into spasm of chewing muscles and respiratory depression. Applied assisted, followed by team breathing. In the next 3 hours after surgery, hypertension and hypercapnia persist. Adult status. Respiratory rate 1-2 per minute.

In this condition, nivaline is administered at a dose of 5 µg subcutaneously. After about 30 πιίη the respiratory rate rises to 12-14 per minute. Echoes the age of majority. There is no evidence of respiratory failure - good respiratory activity and no hypercapnia.

πιίη after re-infiltration of lidocaine (necessitated by the need for revision of the surgical wound), the patient develops a typical clinical picture of intoxication again - motor muscular tremor, chewing muscular trisma, bradypnea and respiratory depression with a frequency of 1-2. After intravenous administration of 2.5 mg § nivaline, all of the above symptoms resolved for 2-3 πιίη. Respiratory rate, neurological status, PaO2, PaCO2, hemoglobin saturation are within normal limits. Following follow-up within the next 6 hours no re-development of toxicity was noted. Life parameters are within normal limits.

Application of the invention

40 patients were monitored. Lidocaine is administered by infiltration local, epidural, spinal and cervical block anesthesia. A scale has been formed to establish the stages in the development of side effects of local anesthetics

In 20 patients (50%) no toxic effect was observed.

In 8 patients / 20% / are reported vegetative changes - dry mouth, perioral, acrocyanosis, cold hands, lack of a pupillary reaction to light, change in the arterial curve.

In 7 patients (17.5%), in addition to the above symptoms and the presence of moderately pronounced tremor of the motor muscles, which is suppressed forcefully, the presence of nystagmus, moderate mental agitation, respiratory rate increase.

In 3 patients / 7.5% / there is a pronounced, discordant tremor of the motor muscles, which cannot be suppressed voluntarily, expressed mental arousal, tachypnea.

In 2 patients / 5% / after a very short period of transient symptoms severe respiratory depression, respiratory distress, hypoareflexia develop.

In a total of 12 patients (30%), different degrees of muscle fibrillation were observed. These patients are administered in gradually increasing doses of 2.5 mg § nivaline until they are completely resolved. The use of nivaline does not affect the analgesic effect of the anesthesia block made. There are no signs of overdose and cholinergic reaction.

Nivalin is most effective in cases of CNS depression and breathing. After administration of 2.5 µl nivaline, a rapid improvement was observed intravenously. The additional fractionated injection of 2.5 lbs leads to the gradual antagonization and restoration of vital functions for 2–3 ιηίη.

The minimum amount of nivaline used to antagonize the toxic effect of lidocaine is 2.5mg. The maximum is 15 lb.

Claims (2)

Use of galanthamine hydrobromide to antagonize the toxic effect of lidocaine. Use of galanthamine hydro10 ' ^and bromide according to claim 1, characterized in that galanthamine hydrobromide is administered in increasing doses from 2.5 gp to 15 gp intravenously, subcutaneously or intramuscularly.