WO2007075100A1 - Method for treating drug dependence - Google Patents

Method for treating drug dependence Download PDF

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Publication number
WO2007075100A1
WO2007075100A1 PCT/RU2005/000674 RU2005000674W WO2007075100A1 WO 2007075100 A1 WO2007075100 A1 WO 2007075100A1 RU 2005000674 W RU2005000674 W RU 2005000674W WO 2007075100 A1 WO2007075100 A1 WO 2007075100A1
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conducted
inhalation
procedure
mixture
sessions
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PCT/RU2005/000674
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French (fr)
Inventor
Sergey Aleksandrovich Naumov
Igor Nikolaevich Roshchin
Aleksandr Nikolaevich Orlov
Grigory Lukich Butakov
Vladimir Petrovich Smetannikov
Olga Alexandrovna Makarova
Sergey Aleksandrovich Shamov
Evgeny Alekseevich Bryun
Vladislav Pavlovich Shcherbak
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Zakrytoe Aktsionernoe Obshchestvo 'atom-Med Center'
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Priority to PCT/RU2005/000674 priority Critical patent/WO2007075100A1/en
Publication of WO2007075100A1 publication Critical patent/WO2007075100A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/10Preparation of respiratory gases or vapours
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/02Gases
    • A61M2202/0208Oxygen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/02Gases
    • A61M2202/0291Xenon

Definitions

  • the invention relates to narcology and anesthesiology and can be used in medical practice to treat drug dependence, including alcoholic dependence, phantom diseases and pains of other genesis.
  • the method of treating the drug dependence closest to the method in the application is withdrawal of the drug, reduction of the abstinence syndrome by anesthetization with concurrent administration of medicinal drugs followed by physiotherapeutic procedures (physiotherapy) and sessions of psychotherapy, the anesthetization being conducted by inhalation of a mixture of oxygen and xenon as an inert gas in a ratio (50 : 50) - (30 : 70) % by volume during 1 - 5 min 1 - 7 times a day during 5 - 7 days (RU no 2165370, 2001).
  • the aim of the present invention is to develop an effective method of treating drug dependence and to expand the arsenal of the methods of treating drug dependence.
  • the technical result ensuring solution of the formulated task is to improve efficacy and to shorten the time of treatment, to improve the immunological status, to exclude recurrence of the abstinence syndrome and narcotic behavior in the process of treatment and induction of the anesthetized condition (full analgesia and amnesia), in order to reduce sharply the emotional and physical discomfort during treatment and thus to reduce the burden on the patient's psyche, apprehension of "pains" resumption, by optimally combining the regimens of administration of the gas-narcotic mixture and extracorporeal hemocorrection, i.e.
  • the method of treating the drug dependence comprises withdrawal of the drug, reduction of the abstinence syndrome by anesthetization alternating with physiotherapy and adiminstration of medicinal drugs, the anesthetization being conducted by inhalation of a gas-narcotic mixture with xenon concentration 20-50 % by volume with the total number of 5-25 sessions, the inhalation being conducted with a mask of the narcotizing apparatus along a semi-open circuit until an adequate level of consciousness suppression is achieved that corresponds to the stage of analgesia and partial amnesia of the inhalation narcosis, but not longer than 10 min, at least one extracorporeal hemocorrection being performed as physiotherapy.
  • Inhalation of the gas-narcotic mixture of oxygen and xenon preferably lasts 3-10 min and the number of sessions per day is gradually reduced, the extracorporeal hemocorrection procedure being conducted not later than two hours before another scheduled inhalation of the gas-narcotic mixture.
  • the extracorporeal hemocorrection procedure at least one plasmapheresis procedure is conducted to eliminate 25-40% of the volume of circulating plasma and compensation of the eliminated plasma with the total volume up to 200%, the plasmapheresis procedure being preceded by therapy or intravenous administration of 1 ,200-2,500 ml of isoosmolar solutions and the eliminated plasma being compensated with a solution containing 70-80% of isoosmolar crystalloid solutions and the eliminated plasma being compensated with a solution containing of isoosmolar crystalloids 20% and a five-percent solution of 0-10% albumin, and/or the extracorporeal hemocorrection procedure being replaced with at least one physiotherapy procedure, such as ultraviolet or laser irradiation of the autoblood in a number of 2 to 7 sessions.
  • physiotherapy procedure such as ultraviolet or laser irradiation of the autoblood in a number of 2 to 7 sessions.
  • a psychotherapeutic session is conducted before or after at least one inhalation of the gas-narcotic mixture.
  • xenon possesses strong psychotropic properties.
  • xenon does not biotransform due to its chemical nature.
  • the effectiveness of its application is determined to a large extent by the rate of diffusion through the mucous membranes and a capacity to interact with the nerve endings in the human respiratory system.
  • the first stage are paresthesia and hypoalgeasia.
  • the second stage are euphoria and psychomotor activity.
  • the third stage are analgesia and partial amnesia. It appears at least after 3 min of inhalation. It is characterized by some consciousness inhibition with pronounced analgesia. Consciousness is partially preserved, yet lethargy intensifies, a premonition of forthcoming full consciousness loss appears. It is possible in the process of inhalation to prolong the analgesia and partial amnesia stage by reducing the in-flow (the gas-narcotic mixture consumption) and to preserve contact with the patient who is able to inform the doctor of the onset of this stage, for example, by moving his hand (or by sound).
  • a fourth stage of anesthesia is possible (full analgesia and amnesia). This stage is not implementable in the pending method.
  • Plasmapheresis is a procedure of extracorporeal hemocorrection envisaging blood separation in a centrifuge into two componental parts: blood bodies and plasma.
  • Plasma is a liquid part of the blood containing no cells and it is an aqueous solution of different proteins. It is exactly the blood plasma that contains a large amount of the toxins not metabolized by the blood cells. Plasma with toxins after centrifuging is decanted and destroyed. The blood cells are returned into the blood system. After that special sterile solutions restore this volume of the liquid.
  • Blood laser irradiation is a procedure of extracorporeal hemocorrection envisaging treatment of the blood through the wall of transparent mass- produced blood carrying lines with a laser emitter and a detachable spherical device attached to the line of the extracorporeal circuit; for this purpose a peripheral vein is punctured or the central vain is catheterized. So there is no- need to introduce a light guide into the bloodstream of the patient, the blood being irradiated without affecting the vascular wall or surrounding tissues.
  • UVI Blood ultraviolet irradiation
  • the main UVI source is usually, for example, a compact quartz lamp with 8 W power. Its emission (84%) belongs predominately to the shortwave range of the spectrum (200-280 nm). To achieve a more even light distribution through the spectrum a light filter is placed between the light source and the bath. Mercury low-pressure lamps can be added to the main lamp with emission concentrating in the long- and middle-wave ranges of the UVI spectrum.
  • the pending method envisages a combination of optimally projected procedures of inhalation and extracorporeal hemocorrection, i.e. physiohemotherapy selected by a method of consecutive approximation and validated empirically.
  • the nervous system is a hierarchic structure of nerve formations in the body and other functions serve to establish contact with the outer world and to coordinate the functions of internal organs, the circulatory system (as the most dynamic one) in the first place and the resulting whole body adaptation.
  • the extracorporeal hemocorrection in the presence of xenon in the body dissolved in lipids as a component of the nervous system ensures faster, more profound changes in the membrane and supramembrane components of the circulating blood cells.
  • erythrocytes The structural changes induced during hemocorrection on the surfaces of erythrocytes, leukocytes and thrombocytes lead to activation of the membrane-dependent processes and the properties of these cells. Since the density of erythrocyte membranes declines the cells become easier deformable, their tendency to aggregate lessens, hence the blood becomes less viscous, its rheological properties and microcirculation improve, the transport of ions and gases through the membranes normalizes. Thrombocytes undergo back aggregation and secrete a broad range of biologically active substances.
  • the population of leukocytes grows by intensification of the phagocytary activity of monocytes and granulocytes, secretion of bacterial cations of proteins, intensification of expression of the receptors of lymphocytes involved in the reaction of rosette formation.
  • the structural and functional changes in plasma proteins reinforce the albumin binding capability, make antibodies and proteins of the system of the complement more active.
  • the effectiveness of the scheduled inhalation of the gas-narcotic mixture of oxygen and inert gas is promoted primarily by high rate of diffusion through mucous membranes and by a possibility of active interaction with nerve endings in the human respiratory system within a period 1-2 hours after extracorporeal hemocorrection is completed, i.e. when changes occur in the plasma proteins and albumin, the activity of antibodies and proteins of the system of the complement grows.
  • the patient familiarizes with the setup text presenting information about the causes and mechanisms of development of drug addiction and disclosing with high degree of detail the sequence of appearance of the symptoms in response to a stage of addiction in such a scope that the patient can be able to evaluate exactly his clinical state and at the same time to conceive how ruinous it is to be drug dependent.
  • the psychic effect on the patient is further reinforced with a curative purpose in the state of wakefulness or hypnosis gradually involving the patient actively into the treatment process convincing that it is most essential to assume responsibility for one's own health realizing that nothing can make man healthy but his own active involvement in the treatment process.
  • Group therapy is admissible when it is conducted with several patients (a group).
  • the psychotherapeutist affects both the group and each participant individually affects another. It favors attention concentration and the amount of perceivable useful information.
  • a patient T 34 years old, body weight 70 kg, body size 170 cm. Admitted for treatment of opium addiction (metadonum) in a state of pronounced opium abstinence.
  • the record of drug consumption is over 15 years. Numerous efforts to get rid of the addiction independently failed. He appealed for medical care for the first time.
  • the concomitant somatic pathology included hypertension, hypertensic crisis at the 2-3 stage, diabetes mellitus of the 2 nd type, toxic cardiomyopathy, toxic hepatitis, multiple metadonum ulcers in the abdominal region, on the upper and lower extremities, fatness of the 3 rd degree.
  • Inhalation therapy was prescribed with a narcotic mixture of oxygen and xenon with the total number of sessions 25. Inhalations were conducted 3 times in the first, second and third days lasting 3-4 minutes with xenon concentration 40% in the mixture, 2 times in the fourth and fifth days lasting 4-5 minutes with xenon concentration 30% in the mixture, consecutive sessions lasted 6-7 minutes daily each once with xenon concentration 20% in the mixture.
  • the eliminated plasma was compensated to ⁇ 200% of the eliminated plasma volume by a solution containing isoosmolar crystalloids 70%, colloids 20% and a five-percent solution of albumin 0-10%.
  • the said infusion therapy was continued.
  • the next extracorporeal hemocorrection procedures were conducted on the 3 rd and 4 th days, vis. two sessions of autoblood ultrasound irradiation.
  • the plasmapheresis procedure was repeated on the fifth day with sampling of 1 ,000 ml of plasma ( ⁇ 30% of the circulating plasma volume) and completed two hours before the scheduled inhalation therapy session.
  • the psychotherapy sessions were conducted daily.
  • the condition at admission was grave: he was acutely inhibited, time and place disoriented, questions were answered with curt phrases.
  • Treatment was prescribed by sessions of inhalation therapy with a gas- narcotic mixture of oxygen and xenon with the total number of sessions 15. Inhalations were conducted 3 times on the first and second days lasting 3-4 minutes with xenon concentration 50% in the mixture, 2 times on the third, fourth and fifth days lasting 5-6 minutes with xenon concentration 35% in the mixture, consecutive sessions lasted 9-10 minutes once a day with xenon concentration 25% in the mixture.
  • the inhalations were conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia and partial amnesia (the 3 rd stage of inhalation narcotization).
  • the inhalations with the oxygen and xenon mixture were combined with daily extracorporeal hemocorrection procedures, or ultrasound autoblood irradiation, with the total number of sessions 7.
  • the extracorporeal hemocorrection procedures were preceded with a clonidine therapy and 1.5 hours after each such procedure a scheduled inhalation therapy session was conducted.
  • the patient was fed parenterally, polyvitamins, antibacterial drugs were administered.
  • a patient 27 years old, body weight 68 kg. Admitted to treat polyaddiction (opiates, alcohol, canabioids). At the moment of admission he consumed over 100 pills of terpincod combined with up to 1 ,000 ml of strong alcoholic drinks a day. The condition was grave at admission. The record of consumption of opiates and alcohol was over 10 years.
  • polyaddiction opiates, alcohol, canabioids
  • condition gravity was due to neurovegetative, psychic, hemodynamic and metabolic disorders within the framework of the abstinence syndrome and toxic hepatitis (the active phase).
  • the eliminated plasma was compensated to ⁇ 180% of the eliminated plasma volume with a solution consisting of isoosmolar crystalloids 80% and colloids 20%.
  • the said infusion therapy was continued.
  • the plasmapheresis procedure was repeated on the 3 rd day of treatment with the same parameters. Each plasmapheresis procedure was completed two hours before the scheduled inhalation therapy session.
  • the markers of toxic hepatitis activity lowered validly on the 5 th day of treatment.
  • a patient D 31 years old, body weight 53 kg. Admitted with a diagnosis of opium addiction, stage II. Consequences of chronic intoxication. Psychic dependence. When addressed he complains of periodic flashes of attraction to drugs, compulsive attraction, dysphoria, depression, sensation of drug lack. He fears to break down and become dependent again. He also presents a complex of psychovegetative complaints.
  • the inhalations were conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia and partial amnesia (the 3 rd stage of inhalation narcotization).
  • Example 5 A female patient X, 24 years of age, was admitted for inpatient treatment with a diagnosis of heroin addiction, abstinence syndrome. Heroin consumption was systematic during the last 5 years, there was no preceding treatment. During admission she complained of pronounced pain in legs, back, poor sleep, anxiety, irritability.
  • the gravity of the condition was due to neurovegetative, psychic, hemodynamic and metabolic disorders within the framework of the abstinence syndrome and toxic hepatitis (the active phase).
  • Treatment was prescribed with inhalation therapy sessions with a gas-narcotic mixture of oxygen and xenon with a total number of sessions 20.
  • the inhalations were conducted 3 times a day during the first and second days lasting 3-4 minutes with xenon concentration 45% in the mixture, 3 times a day during the third and fourth days lasting 4-5 minutes with xenon concentration 30% in the mixture, 2 times a day during the fifth and sixth days lasting 5-6 minutes with xenon concentration 25% in the mixture, further sessions lasted 7-8 minutes once daily with xenon concentration 20% in the mixture.
  • the inhalations were conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia and partial amnesia reported to the doctor by a hand movement (the third stage of inhalation narcotization).
  • the abstinence syndrome, explosive, affective and dyssomniac disorders were reduced.
  • Ten hours after admission an extracorporeal hemocorrection procedure was conducted, vis. gravitational plasmapheresis with plasma sampling in a quantity of 900 ml ( ⁇ 25% of the circulating plasma volume) completed two hours before the scheduled infusion therapy session.
  • the infusion therapy by intravenous administration of 1 ,200 ml of isoosmolar crystalloids with addition of clonidine, disaggregants, spasmolytics and vitamins was conducted beforehand.
  • the eliminated plasma was compensated for ⁇ 180% of the eliminated plasma volume with a solution containing isoosmolar crystalloids 80%, colloids 20% and a five-percent solution of albumin 10%.
  • the said infusion therapy was continued. After six inhalations and the first plasmapheresis session the vegetative dysfunctions (hyperhydrosis, pulling pains in joints and muscles, unstable hemodynamics) were eliminated.
  • the following hemocorrection procedures were conducted on the third and fourth days: two sessions of laser autoblood irradiation each completed two hours before the scheduled inhalation therapy session.
  • the psychotherapy sessions were conducted daily starting on the eleventh day.
  • the efficacy of treatment of the immunity status has been improved and its term reduced, the abstinence syndrome recurrence and narcotic behavior in the process of treatment have been prevented, the condition of anesthesia of the patient has been induced (full analgesia and amnesia) so that the emotional and physical discomfort in the course of conducted treatment is sharply relieved and so is the burden on the patient' psyche fearing recurrence of "pains" by an optimum combination of regimens of administration of the gas-narcotic mixture and extracorporeal hemocorrection, i.e. implementation of complex therapy corresponding to the hierarchic structure of the human organism and the need of multilevel effect to achieve a stable (irreversible) result within an optimum term.
  • the systemic metabolic processes are not affected or inhibited in the organism, the immunity and vital functions are activated with a relatively weak traumatizing procedures of inhalation of the gas-narcotic mixture and extracorporeal hemocorrection and simultaneous sharp reduction of the drug, burden on the patient.

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Abstract

The method of treating drug dependence comprising drug withdrawal, abstinence syndrome reduction by anesthetization alternating with physiotherapy and administration of medicinal drugs, the anesthetization being conducted with inhalation of a gas-narcotic mixture of oxygen and xenon with xenon concentration in the mixture being 20-50 % by volume and the total number of sessions 5-25, with the inhalation being conducted until the level of consciousness inhibition is reached corresponding to the stage of analgesia or partial amnesia by inhalation narcotization and by gradual reduction of the number of sessions per day, and at least one procedure of extracorporeal hemocorrection being conducted as physiotherapy not Iater than two hours before its completion a scheduled session of inhalation of the gas-narcotic mixture being administered. One procedure of plasmapheresis and\or ultraviolet and laser autoblood irradiation in a number of 2 to 7 sessions is conducted as the procedure of extracorporeal hemocorrection. The result is improvement of the efficacy and reduction of the duration of treatment, improvement of the immunological status, prevention of the abstinence syndrome and narcotic behavior recurrence in the process of treatment. The systemic metabolic processes are not affected or inhibited; the immunity and vital functions are activated with a relatively weak traumatizing effect of inhalation of the gas-narcotic mixture and extracorporeal hemocorrection and simultaneous sharp relief of the drug burden on the patient.

Description

METHOD OF TREATING DRUG DEPENDENCE Field of the Invention
The invention relates to narcology and anesthesiology and can be used in medical practice to treat drug dependence, including alcoholic dependence, phantom diseases and pains of other genesis.
Drug dependence manifests itself in narcotic behavior and percieved by man in the following forms:
• permanent and obsessive ideas of drug consumption; • suppression of the desire to consume a drug;
• depression, aggressiveness in respect to oneself or others;
• mood variations;
• insomnia;
• drug-induced dreams; • feelings of despair of living a drug-dependent life and futility of undertaking any effort of treatment;
• self-humiliation for lack of will;
• the syndrome of abstinence, one of the gravest manifestations of the disease for the patient. A menace of evolution of abstinence (pains) is frequently a cause of continuation of drugs abuse. In many cases a chance to eliminate the syndrome of abstinence determines the efficacy of treatment in general. However, even administration of modern pain-killers, tranquilizers or antidepressants in large doses fails to subdue all tormenting sensations of the abstinence syndrome during many days. It necessitates improvement of the arsenal of treatment methods.
There is a method of treating drug dependence including withdrawal of the drug, reduction of the abstinence syndrome by anesthetization concurrently with administration of medicinal drugs followed by physiotherapeutic procedures and sessions of psychotherapy. Besides, after drug withdrawal, large doses of antagonists (naloxonum, naltrexonum) are administered for intensive elimination of the exogenous opiates from the central nervous system and from the organism in general. The emerging abstinence syndrome is reduced with traditional anesthetics (nitrogen peroxide, etc.) by endotracheal anesthesia and artificial pulmonary ventilation during many hours (6-8 h). If necessary, medicinal drugs (for example, those to support the cardiac function, to suppress pathological vegetative reactions, etc.) are administered concurrently with anesthetization or before it [c.f. A.V. Bugrov, S. G. Tsimbalov, Ultrarapid Opioid Detoxication, Medical Files (in Russian, no 1 , p. 32]. The shortcomings of the method are the following:
- poor treatment efficacy (a large probability of relapses);
- the period of the treatment necessary to eliminate the abstinence syndrome is too long;
- harmful effect of large doses of medicinal drugs and anesthetics metabolizing in the liver; severe traumatism due to the need of intubation. Due to this some patients refuse the treatment and cannot get rid of painfulful sensation for a long time and tend to their immediate elimination by any means (including resumption of drug consumption).
The method of treating the drug dependence closest to the method in the application is withdrawal of the drug, reduction of the abstinence syndrome by anesthetization with concurrent administration of medicinal drugs followed by physiotherapeutic procedures (physiotherapy) and sessions of psychotherapy, the anesthetization being conducted by inhalation of a mixture of oxygen and xenon as an inert gas in a ratio (50 : 50) - (30 : 70) % by volume during 1 - 5 min 1 - 7 times a day during 5 - 7 days (RU no 2165370, 2001). The shortcomings of this method are poor efficacy of treatment due to periodic recurrence of the abstinence syndrome in the process of treatment creating an extra stress for the patient's psyche, permanent apprehension of "pains" resumption and due to a non-optimal inhalation regimen and a non- optimal combination of administration of the gas-narcotic mixture and physiotherapy. Due to this some patients reject treatment that permits painful sensation of the abstinence syndrome to resume and tend to eliminate them immediately by any means (even by resuming drugs consumption). Background of the Invention
The aim of the present invention is to develop an effective method of treating drug dependence and to expand the arsenal of the methods of treating drug dependence.
The technical result ensuring solution of the formulated task is to improve efficacy and to shorten the time of treatment, to improve the immunological status, to exclude recurrence of the abstinence syndrome and narcotic behavior in the process of treatment and induction of the anesthetized condition (full analgesia and amnesia), in order to reduce sharply the emotional and physical discomfort during treatment and thus to reduce the burden on the patient's psyche, apprehension of "pains" resumption, by optimally combining the regimens of administration of the gas-narcotic mixture and extracorporeal hemocorrection, i.e. by implementing a complex therapy in accordance with the hierarchical structure of the human organism and the need of multilevel effect in order to achieve a stable (irreversible) result within an optimum time. At the same time there is no negative effect on metabolic processes in the organism, its immunity and vital functions are activated with a comparatively weak traumatism of the inhalation procedures with the gas-narcotic mixture and extracorporeal hemocorrection with simultaneous sharp reduction of the drug burden on the patient.
Invention disclosure The essence of the invention is that the method of treating the drug dependence comprises withdrawal of the drug, reduction of the abstinence syndrome by anesthetization alternating with physiotherapy and adiminstration of medicinal drugs, the anesthetization being conducted by inhalation of a gas-narcotic mixture with xenon concentration 20-50 % by volume with the total number of 5-25 sessions, the inhalation being conduced with a mask of the narcotizing apparatus along a semi-open circuit until an adequate level of consciousness suppression is achieved that corresponds to the stage of analgesia and partial amnesia of the inhalation narcosis, but not longer than 10 min, at least one extracorporeal hemocorrection being performed as physiotherapy.
Inhalation of the gas-narcotic mixture of oxygen and xenon preferably lasts 3-10 min and the number of sessions per day is gradually reduced, the extracorporeal hemocorrection procedure being conducted not later than two hours before another scheduled inhalation of the gas-narcotic mixture.
As the extracorporeal hemocorrection procedure at least one plasmapheresis procedure is conducted to eliminate 25-40% of the volume of circulating plasma and compensation of the eliminated plasma with the total volume up to 200%, the plasmapheresis procedure being preceded by therapy or intravenous administration of 1 ,200-2,500 ml of isoosmolar solutions and the eliminated plasma being compensated with a solution containing 70-80% of isoosmolar crystalloid solutions and the eliminated plasma being compensated with a solution containing of isoosmolar crystalloids 20% and a five-percent solution of 0-10% albumin, and/or the extracorporeal hemocorrection procedure being replaced with at least one physiotherapy procedure, such as ultraviolet or laser irradiation of the autoblood in a number of 2 to 7 sessions.
A psychotherapeutic session is conducted before or after at least one inhalation of the gas-narcotic mixture.
To implement the pending method the medical xenon (TR 1473-004-
39931507-2000) allowed for use as an anesthetic by the Russian Ministry of Public Health entered into the State Register of medicinal drugs under registration no 99/363/4, provisional Pharmacopoeia Article 42-2891-97 approved 10\08\99.
Repeated experimental and clinical studies prove that xenon possesses strong psychotropic properties. By dissolving in the lipids of the organism as a component of the nervous system, xenon does not biotransform due to its chemical nature. The effectiveness of its application is determined to a large extent by the rate of diffusion through the mucous membranes and a capacity to interact with the nerve endings in the human respiratory system.
As a result, it is not toxic, produces no side or carcinogenic, allergic or cardiodepressive effects, it does not affect the composition and blood coagulation system, immunity, it is environmentally clean and safe to a patient and the attending personnel and has no counterindications for medical practice.
Four stages of oxygen-xenon inhalation have been revealed.
The first stage are paresthesia and hypoalgeasia. The second stage are euphoria and psychomotor activity.
The third stage are analgesia and partial amnesia. It appears at least after 3 min of inhalation. It is characterized by some consciousness inhibition with pronounced analgesia. Consciousness is partially preserved, yet lethargy intensifies, a premonition of forthcoming full consciousness loss appears. It is possible in the process of inhalation to prolong the analgesia and partial amnesia stage by reducing the in-flow (the gas-narcotic mixture consumption) and to preserve contact with the patient who is able to inform the doctor of the onset of this stage, for example, by moving his hand (or by sound).
A fourth stage of anesthesia is possible (full analgesia and amnesia). This stage is not implementable in the pending method.
The patient re-awakens, as a rule, 4-5 minutes after inhalation of the oxygen- xenon mixture is discontinued; his consciousness fully restores 4-5 minutes afterwards.
Plasmapheresis is a procedure of extracorporeal hemocorrection envisaging blood separation in a centrifuge into two componental parts: blood bodies and plasma. Plasma is a liquid part of the blood containing no cells and it is an aqueous solution of different proteins. It is exactly the blood plasma that contains a large amount of the toxins not metabolized by the blood cells. Plasma with toxins after centrifuging is decanted and destroyed. The blood cells are returned into the blood system. After that special sterile solutions restore this volume of the liquid.
Blood laser irradiation is a procedure of extracorporeal hemocorrection envisaging treatment of the blood through the wall of transparent mass- produced blood carrying lines with a laser emitter and a detachable spherical device attached to the line of the extracorporeal circuit; for this purpose a peripheral vein is punctured or the central vain is catheterized. So there is no- need to introduce a light guide into the bloodstream of the patient, the blood being irradiated without affecting the vascular wall or surrounding tissues. As a rule, the following regimens of blood extracorporeal laser irradiation are observed: the extracorporeal blood flow rate - 100 ml/min, duration of irradiation - 30 min, power of irradiation - 4 mW, frequency - 1 ,500 Hz. Blood ultraviolet irradiation (UVI) is a procedure of extracorporeal hemocorrection envisaging photomodification of the patient's circulating blood in the quartz bath built into an extracorporeal vein-venous or vein- arterial circuit.
The main UVI source is usually, for example, a compact quartz lamp with 8 W power. Its emission (84%) belongs predominately to the shortwave range of the spectrum (200-280 nm). To achieve a more even light distribution through the spectrum a light filter is placed between the light source and the bath. Mercury low-pressure lamps can be added to the main lamp with emission concentrating in the long- and middle-wave ranges of the UVI spectrum.
The pending method envisages a combination of optimally projected procedures of inhalation and extracorporeal hemocorrection, i.e. physiohemotherapy selected by a method of consecutive approximation and validated empirically. To outline the direction of studies it was assumed that the nervous system is a hierarchic structure of nerve formations in the body and other functions serve to establish contact with the outer world and to coordinate the functions of internal organs, the circulatory system (as the most dynamic one) in the first place and the resulting whole body adaptation. Hence, the extracorporeal hemocorrection in the presence of xenon in the body dissolved in lipids as a component of the nervous system ensures faster, more profound changes in the membrane and supramembrane components of the circulating blood cells. The structural changes induced during hemocorrection on the surfaces of erythrocytes, leukocytes and thrombocytes lead to activation of the membrane-dependent processes and the properties of these cells. Since the density of erythrocyte membranes declines the cells become easier deformable, their tendency to aggregate lessens, hence the blood becomes less viscous, its rheological properties and microcirculation improve, the transport of ions and gases through the membranes normalizes. Thrombocytes undergo back aggregation and secrete a broad range of biologically active substances. The population of leukocytes grows by intensification of the phagocytary activity of monocytes and granulocytes, secretion of bacterial cations of proteins, intensification of expression of the receptors of lymphocytes involved in the reaction of rosette formation. The structural and functional changes in plasma proteins reinforce the albumin binding capability, make antibodies and proteins of the system of the complement more active. The effectiveness of the scheduled inhalation of the gas-narcotic mixture of oxygen and inert gas is promoted primarily by high rate of diffusion through mucous membranes and by a possibility of active interaction with nerve endings in the human respiratory system within a period 1-2 hours after extracorporeal hemocorrection is completed, i.e. when changes occur in the plasma proteins and albumin, the activity of antibodies and proteins of the system of the complement grows.
During psychotherapy the patient familiarizes with the setup text presenting information about the causes and mechanisms of development of drug addiction and disclosing with high degree of detail the sequence of appearance of the symptoms in response to a stage of addiction in such a scope that the patient can be able to evaluate exactly his clinical state and at the same time to conceive how ruinous it is to be drug dependent. The psychic effect on the patient is further reinforced with a curative purpose in the state of wakefulness or hypnosis gradually involving the patient actively into the treatment process convincing that it is most essential to assume responsibility for one's own health realizing that nothing can make man healthy but his own active involvement in the treatment process. Group therapy is admissible when it is conducted with several patients (a group). The psychotherapeutist affects both the group and each participant individually affects another. It favors attention concentration and the amount of perceivable useful information.
Detailed Description of the Invention
Example 1
A patient T, 34 years old, body weight 70 kg, body size 170 cm. Admitted for treatment of opium addiction (metadonum) in a state of pronounced opium abstinence. The record of drug consumption is over 15 years. Numerous efforts to get rid of the addiction independently failed. He appealed for medical care for the first time. By the time of admission he injected daily 2.0 grams of freely sold metadonum intramuscularly. The concomitant somatic pathology included hypertension, hypertensic crisis at the 2-3 stage, diabetes mellitus of the 2nd type, toxic cardiomyopathy, toxic hepatitis, multiple metadonum ulcers in the abdominal region, on the upper and lower extremities, fatness of the 3rd degree.
After admission the sources of the drug were excluded (the drug withdrawal). Inhalation therapy was prescribed with a narcotic mixture of oxygen and xenon with the total number of sessions 25. Inhalations were conducted 3 times in the first, second and third days lasting 3-4 minutes with xenon concentration 40% in the mixture, 2 times in the fourth and fifth days lasting 4-5 minutes with xenon concentration 30% in the mixture, consecutive sessions lasted 6-7 minutes daily each once with xenon concentration 20% in the mixture. Inhalations were conducted with a mask of the narcotizing, apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia (the third stage of inhalation narcotization); the patient informed the doctor of the fact by moving his hand; afterwards the mixture consumption was reduced by 25-30% until the end of the session, if the session was to be continued to maintain the third stage and to prevent transition to the fourth narcotization stage. Explosive, affective and dyssomniac disturbances were thus reduced.
Twelve hours after admission the procedure of extracorporeal hemocorrection was conducted, vis. gravitational plasmapheresis with plasma sampling in a quantity of 1 ,400 ml (~ 40% of the circulating plasma volume) that was completed two hours before another inhalation therapy session. Beforehand an infusion therapy was conducted by intravenous infusion of 2,500 ml of isoosmolar crystalloids per day in electrolytic solutions with addition of medicinal preparation of clonidine, disaggregants, spasmolytics, vitamins.
The eliminated plasma was compensated to ~ 200% of the eliminated plasma volume by a solution containing isoosmolar crystalloids 70%, colloids 20% and a five-percent solution of albumin 0-10%. The said infusion therapy was continued. After three inhalations and the first plasmapheresis procedure stabilization of the vegetative dysfunctions was observed (hyperhydrosis, pulling ache in joints and muscles, unstable hemodynamics were eliminated). The next extracorporeal hemocorrection procedures were conducted on the 3rd and 4th days, vis. two sessions of autoblood ultrasound irradiation. The plasmapheresis procedure was repeated on the fifth day with sampling of 1 ,000 ml of plasma (~ 30% of the circulating plasma volume) and completed two hours before the scheduled inhalation therapy session. Starting on the ninth day the psychotherapy sessions were conducted daily.
As a result the abstinence syndrome was reduced practically completely, the signs of secondary immunodeficit and trophic disorders were reduced. Obsessive ideas about drug consumption did not recur after the conducted treatment, the sleep normalized on the 9th day, the remaining manifestations of drug dependence were absent.
The patient was discharged on the 22nd day in a satisfactory condition and advised to use blockers of opium receptors (antaxonum). Examination 1 month afterwards showed satisfactory condition, abstinence from drug consumption. Example 2
A patient Ya., 55 years old, body weight - 65 kg . Hospitalized with the diagnosis of alcoholism in the 3rd stage, encephalopathy of a complex genesis (toxic, vascular), Korsakoff's psychosis, polyneuropathy, acute right upper lobar pneumonia in the stage of resolution, CHD. Atherosclerotic cardiosclerosis, alcoholic cardiomyopathy.
The condition at admission was grave: he was acutely inhibited, time and place disoriented, questions were answered with curt phrases.
When collecting the anamnesis it was revealed that the patient for a long time (over 20 years) abused alcohol. Drinking was continuous during the last 5 years. During the last four years the alcohol abstinence was aggravated with epileptic fits. The patient worked as a surgeon, a candidate of medical science, an assistant professor, dealing with treatment and education. He had been a consulting doctor at a pediatric clinic during the last five years.
He was concealing his alcohol dependence from others, never appealed for any narcological care. Before admission at the neurological ward his relatives found him at home unconscious and that motivated his hospitalization.
Treatment was prescribed by sessions of inhalation therapy with a gas- narcotic mixture of oxygen and xenon with the total number of sessions 15. Inhalations were conducted 3 times on the first and second days lasting 3-4 minutes with xenon concentration 50% in the mixture, 2 times on the third, fourth and fifth days lasting 5-6 minutes with xenon concentration 35% in the mixture, consecutive sessions lasted 9-10 minutes once a day with xenon concentration 25% in the mixture.
The inhalations were conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia and partial amnesia (the 3rd stage of inhalation narcotization). Starting since the 2nd day of treatment the inhalations with the oxygen and xenon mixture were combined with daily extracorporeal hemocorrection procedures, or ultrasound autoblood irradiation, with the total number of sessions 7. The extracorporeal hemocorrection procedures were preceded with a clonidine therapy and 1.5 hours after each such procedure a scheduled inhalation therapy session was conducted.
Also, the patient was fed parenterally, polyvitamins, antibacterial drugs were administered.
Stabilization of hemodynamics and respiration indices, muscular relaxation, and sound sleep during 3-4 hours were observed after each inhalation therapy session.
Starting since the fifth day of the conducted complex therapy distinct positive dynamics of clinical and laboratory indices were observed:
- the indices of hemodynamics, gas exchange, clinical and biochemical blood indices stabilized;
- the roentgenography showed reduction of inflammatory changes in the lungs;
- the radiography and cardiography registered improvement of myocardium and brain blood supply; - the patient retrieved capability to move around the ward unassisted and to service himself;
- the patient became more active in the daytime and his night sleep normalized;
- his speech became more distinct and emotional; - his memory of past and current events improved distinctly, the professional memory was the first to restore;
- a critical approach to his condition and a desire to recover appeared. Starting since the 7th day the psychotherapy sessions were conducted every second day. On the 16th day the patient was transferred to the narcological ward where vitaminotherapy, exercise- and psychotherapies were continued. As a result the abstinence syndrome was practically completely reduced, after conducted treatment the obsessive thoughts about drug consumption did not re-appear, there were no other manifestations of drug dependence. He was discharged in a satisfactory condition. Examination 12 months later: the condition is satisfactory, no consumption of narcotic substances. Example 3.
A patient, 27 years old, body weight 68 kg. Admitted to treat polyaddiction (opiates, alcohol, canabioids). At the moment of admission he consumed over 100 pills of terpincod combined with up to 1 ,000 ml of strong alcoholic drinks a day. The condition was grave at admission. The record of consumption of opiates and alcohol was over 10 years.
The condition gravity was due to neurovegetative, psychic, hemodynamic and metabolic disorders within the framework of the abstinence syndrome and toxic hepatitis (the active phase).
He was prescribed inhalation therapy sessions with a narcotic mixture of oxygen and xenon with the total number of sessions 10.
Inhalations were conducted 4 times during the first three days and lasted 3-4 minutes with xenon concentration 45% in the mixture, then 2 times during the next 7 days lasting 5-7 minutes with xenon concentration 25% in the mixture.
Inhalations were conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia and partial amnesia (the 3rd stage of inhalation narcotization).
After preparation during a day including compensation of liquid deficit, correction of gross hemodynamic and electrolytic disorders, initial clonidine therapy, an extracorporeal hemocorrection procedure was gravitational plasmapheresis with plasma sampling in a quantity 1 ,250 ml (~ 35% of the circulating plasma volume). Infusion therapy was conducted in advance, or intravenous infusion of 1 ,200 ml of isoosmolar crystalloids a day in electrolytic solutions with addition of medicinal preparations of clonidine, spasmolytics and vitamins.
The eliminated plasma was compensated to ~ 180% of the eliminated plasma volume with a solution consisting of isoosmolar crystalloids 80% and colloids 20%. The said infusion therapy was continued.
The plasmapheresis procedure was repeated on the 3rd day of treatment with the same parameters. Each plasmapheresis procedure was completed two hours before the scheduled inhalation therapy session.
As a result of the conducted treatment the pain syndrome and the compulsive attraction to psychoactive substances were completely reduced on the 3rd day, the enzymetemia and bilurubinemia were eliminated by the seventh day together with the clinical presentation of hepatic encephalopathy, a distinct reduction of psychopathic (emotional labiality, irritation weakness, dysphoria and dyssomnia) and neurovegetative (hyperhydrosis, tremor, orthostatic variations of hemodynamics, etc.) symptomatology.
The markers of toxic hepatitis activity lowered validly on the 5th day of treatment.
As a result the abstinence syndrome was practically completely reduced, after conducted treatment the obsessive thoughts about drug consumption did not re-appear, there were no other manifestations of drug dependence. He was discharged in a satisfactory condition.
On the 12th day the patient was transferred to the narcological ward in a satisfactory condition for further psychotherapy and medico-social rehabilitation. He was discharged in a satisfactory condition.
Examination 10 months later: the condition is satisfactory, no consumption of narcotic substances.
Example 4.
A patient D, 31 years old, body weight 53 kg. Admitted with a diagnosis of opium addiction, stage II. Consequences of chronic intoxication. Psychic dependence. When addressed he complains of periodic flashes of attraction to drugs, compulsive attraction, dysphoria, depression, sensation of drug lack. He fears to break down and become dependent again. He also presents a complex of psychovegetative complaints.
He was prescribed treatment with inhalation therapy sessions with a gas-narcotic mixture of oxygen and xenon with the total number of sessions 5.
Inhalations were conducted once a day and lasted 6-7 minutes with xenon concentration 20% in the mixture.
The inhalations were conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia and partial amnesia (the 3rd stage of inhalation narcotization).
Starting since the 2nd day of treatment the inhalations with the oxygen and xenon mixture were combined with daily extracorporeal hemocorrection procedures, or ultrasound autoblood irradiation, with the total number of two sessions. The extracorporeal hemocorrection procedures were preceded with a clonidine therapy and 1.5 hours following each such procedure a scheduled inhalation therapy session was conducted.
As a result of the conducted treatment the pain syndrome and the compulsive attraction to psychoactive substances were completely reduced on the 3rd day, and by the seventh day together with the clinical presentation of a distinct reduction of psychopathological (emotional labiality, irritation weakness, dysphoria and dyssomnia) and neurovegetative (hyperhydrosis, tremor, orthostatic variations of hemodynamics, etc.) symptomatology. Psychotherapy sessions were conducted daily starting after the 7th day. As a result the abstinence syndrome was practically completely reduced
(no complaints), the obsessive thoughts about drug consumption did not reappear, there were no other manifestations of drug dependence.
On the 11 th day the patient was transferred to the narcological ward in a satisfactory condition for further psychotherapy and medico-social rehabilitation. He was discharged in a satisfactory condition.
Examination 12 months later: the condition is satisfactory, no consumption of narcotic substances. Example 5. A female patient X, 24 years of age, was admitted for inpatient treatment with a diagnosis of heroin addiction, abstinence syndrome. Heroin consumption was systematic during the last 5 years, there was no preceding treatment. During admission she complained of pronounced pain in legs, back, poor sleep, anxiety, irritability.
The gravity of the condition was due to neurovegetative, psychic, hemodynamic and metabolic disorders within the framework of the abstinence syndrome and toxic hepatitis (the active phase).
Since the moment of admission for treatment the drug sources were eliminated (drug withdrawal). Treatment was prescribed with inhalation therapy sessions with a gas-narcotic mixture of oxygen and xenon with a total number of sessions 20. The inhalations were conducted 3 times a day during the first and second days lasting 3-4 minutes with xenon concentration 45% in the mixture, 3 times a day during the third and fourth days lasting 4-5 minutes with xenon concentration 30% in the mixture, 2 times a day during the fifth and sixth days lasting 5-6 minutes with xenon concentration 25% in the mixture, further sessions lasted 7-8 minutes once daily with xenon concentration 20% in the mixture.
The inhalations were conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition was reached corresponding to the stage of analgesia and partial amnesia reported to the doctor by a hand movement (the third stage of inhalation narcotization). The abstinence syndrome, explosive, affective and dyssomniac disorders were reduced. Ten hours after admission an extracorporeal hemocorrection procedure was conducted, vis. gravitational plasmapheresis with plasma sampling in a quantity of 900 ml (~ 25% of the circulating plasma volume) completed two hours before the scheduled infusion therapy session. The infusion therapy by intravenous administration of 1 ,200 ml of isoosmolar crystalloids with addition of clonidine, disaggregants, spasmolytics and vitamins was conducted beforehand. The eliminated plasma was compensated for ~ 180% of the eliminated plasma volume with a solution containing isoosmolar crystalloids 80%, colloids 20% and a five-percent solution of albumin 10%. The said infusion therapy was continued. After six inhalations and the first plasmapheresis session the vegetative dysfunctions (hyperhydrosis, pulling pains in joints and muscles, unstable hemodynamics) were eliminated. The following hemocorrection procedures were conducted on the third and fourth days: two sessions of laser autoblood irradiation each completed two hours before the scheduled inhalation therapy session. The psychotherapy sessions were conducted daily starting on the eleventh day.
As a result the abstinence syndrome was practically completely reduced; the signs of secondary immunodeficit and trophic disorders were reduced. The obsessive thoughts about drug consumption did not re-appear after the conducted treatment, the sleep normalized on the eighth day; there were no other manifestations of drug dependence.
She was discharged in a satisfactory condition on the 20th day and advised to use blockers of opium receptors (antaxonum). Examination 15 months later revealed a satisfactory condition, no consumption of narcotic substances. Thus, an effective method of treating drug dependence has been developed and an arsenal of methods of treating drug dependence has been expanded.
Also, the efficacy of treatment of the immunity status has been improved and its term reduced, the abstinence syndrome recurrence and narcotic behavior in the process of treatment have been prevented, the condition of anesthesia of the patient has been induced (full analgesia and amnesia) so that the emotional and physical discomfort in the course of conducted treatment is sharply relieved and so is the burden on the patient' psyche fearing recurrence of "pains" by an optimum combination of regimens of administration of the gas-narcotic mixture and extracorporeal hemocorrection, i.e. implementation of complex therapy corresponding to the hierarchic structure of the human organism and the need of multilevel effect to achieve a stable (irreversible) result within an optimum term. The systemic metabolic processes are not affected or inhibited in the organism, the immunity and vital functions are activated with a relatively weak traumatizing procedures of inhalation of the gas-narcotic mixture and extracorporeal hemocorrection and simultaneous sharp reduction of the drug, burden on the patient.

Claims

1. A method of treating drug dependence comprising drug withdrawal, abstinence syndrome reduction by anesthetization alternating with physiotherapy and administration of medicinal drugs, the anesthesia being conducted by inhalation of a gas-narcotic mixture of oxygen and xenon with xenon concentration in the mixture 20-50 % by volume and the total number of sessions 5-25, the inhalation being conducted with a mask of the narcotizing apparatus along a semi-open circuit until the level of consciousness inhibition is reached corresponding to the stage of analgesia and partial amnesia by inhalation narcotization but not longer than 10 min, at least one procedure of extracorporeal hemocorrection being conducted as physiotherapy.
2. The method, according to Claim 1 , characterized in that inhalation of the gas-narcotic mixture of oxygen and xenon being conducted during 3-10 min gradually prolonging it and reducing the number of sessions per day, meanwhile the extracorporeal hemocorrection procedure being conducted not more than two hours before inhalation of the gas-narcotic mixture.
3. The method, according to Claim 1 or Claim 2, characterized in that by which at least one procedure of plasmapheresis being conducted as the procedure of extracorporeal hemocorrection with elimination of 25-40% of the circulating plasma volume and compensation of the eliminated plasma with a total volume up to 200%,
4. . The method, according to Claim 1 , characterized in that by which a preliminary therapy being conducted before the procedure of plasmapheresis by intravenous infusion of 1 ,200-2,500 ml of solutions of isoosmolar crystalloids and the eliminated plasma being compensated with a solution containing isoosmolar crystalloids 70-80%, colloids 20% and a five- percent solution of albumin 0-10%.
5. . The method, according to Claim 1 or Claim 2, characterized in that by which one session of ultraviolet or laser autoblood irradiation procedure in the number of 2 to 7 sessions being conducted as an extracorporeal hemocorrection procedure.
6. . The method, according to Claim 1 or Claim 2, characterized in that by which one psychotherapy session being conducted before or after at least one inhalation of the gas-narcotic mixture.
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Citations (3)

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RU2226408C2 (en) * 2001-05-14 2004-04-10 Отделение "Новые медицинские технологии" Государственного унитарного дочернего предприятия Научно-исследовательского и конструкторского института энерготехники Техноцентр "Лазерная диагностика и чистая технология" Method for treating narcomania patients for acute abstinence syndrome

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