02:33 Ultra Rapid Opioid Detoxification UROD (AMLO) | |
| In recent years, large-spread drug addiction caused by the abuse of opium, its alkaloids and synthetic substitutes.
Among opioids occupies a special place heroin abuse which leads to
serious consequences and heroin withdrawal is particularly heavy. The discovery of opioid receptors and their endogenous ligands allowed to approach the problem of the treatment of opiate addiction pathophysiological, specify the existing expertise and find a more reliable treatments. Different parts of the brain ensure the implementation of specific information. Inside the limbic system of the brain highlighted system that are activated when a person receiving a positive reinforcer. This system is called a system of pleasure and reward - "reward" [6]. Pathways reward-systems start from ventral tegmental area (VTA), concentrated in the nucleus accumbens and prefrontal cortical end in the area (listed only those structures that reward-system bear the greatest functional loading). Natural stimulant reward-system is food, sex, water, education and others. The result of activation of reward system - test the feelings of pleasure and desire to repeat this many times incentive [6]. VTA neurons contain the neurotransmitter dopamine that is released in the nucleus accumbens and prefrontal cortical region. With stimulation of VTA is enhanced not only dopaminergic neurotransmission [17]. By numerous dendritic and aksosomalnyh links are activated noradrenergic, GABAergic, opioid, serotonergic, cholinergic and other types of neurons in a variety of structural and functional systems of the brain. But human behavior, aimed at having fun, dopamine is the main component. [17] The reward-system opioid receptors (mainly the mu and kappa) presynaptically located in relation to the dopaminergic synapse and have a stimulating effect, acting as a modulator [3]. Normally, the opioid receptor agonists are endogenous opioids: leukemia and metenkefaliny and dynorphin. It should be noted that the quantitative and qualitative ratio of mu, kappa and delta receptors in the reward-structures of the system, according to the literature, is not precisely defined [5,20]. Experimental and clinical data suggest a greater version that mu and kappa receptors are coupled [5]. The point of application of narcotic drugs and the abuse associated with the structures of the brain outside the reward-system, and the mechanism of the desired result ("high", "arrival", etc.) with increased dopaminergic neurotransmission [5.17]. Since Ultrafast detoxification is used mainly when heroin addiction, consider the effect of exogenous opioids on dopaminergic transmission. Casual tonic stimulation of endogenous enkephalins opioid receptors located presynaptically against the dopaminergic synapse determines strictly individual level of dopamine release in quantitative terms, which is the norm for everyone. Acute morfinizatsiya reduces the release of dopamine in quantitative terms, which reduces the metabolism of the postsynaptic nerve cell and causes a state of inhibition of CNS neyrolepsiyu [3]. Chronic morfinizatsiya a new receptor-metabolic relationship under which a state opioidnozavisimoy standards. In chronic administration of exogenous opioid dopamine-containing vacuoles are concentrated closer to the presynaptic membrane that accelerates their release, but to quantify dopamine content mezhsinapticheskoy gap decreases [1]. Last compensated by the development of hypersensitivity of dopamine receptors. To reduce the emission of dopamine reception with chronic exogenous opioids is necessary to involve a larger number of opioid receptors of presynaptic, that means an increase in the dose of the drug to produce the effect of "high". [3] Blockade opioid receptor antagonist (naloxone, naltrexone nalmefin) due to chronic opioid use and release of dopamine is increased postsynaptic nerve cell is in the state of hypermetabolism (magnification of 5 times with respect to the source), lasting after administration of naloxone 5-6 hours. The decreased cell metabolism, but is increased by 2 times. The reason for hypermetabolism during the liberation of the opioid receptor agonist, competitive antagonist is associated with both an increased release of dopamine and a dopamine receptor giperchustvitelnostyu unused [3]. The dopaminergic transmission postsynaptic nerve cell can in principle be of any type (GABAergic, serotonergic, acetylcholinergic, noradrenaline) [20]. Studies show that the density of noradrenergic neurons and dopamine, noradrenaline somatodendricheskih links above in reward-system, which leads to a greater degree to the hypermetabolic it noradrenergic neurons. Increased noradrenergic neurotransmission and causes most of the symptoms of withdrawal syndrome [7]. In specific dopaminergic neurons vnutrisinapticheskogo places inhibition found. In the neuron noradrenaline exists a physiological mechanism of inhibition by alpha 2-adrenergic receptors located on the presynaptic terminal inside the synapse. Physiological agonists adrenergic neurons is noradrenaline itself. They are exogenous agonists clonidine, guanfacine. Both drugs stimulate both postsynaptic (alpha1-adrenergic receptor) and presynaptic inhibitory alpha2-adrenergic. But tropism for alpha2-adrenergic receptor is higher, so the net effect is inhibition of noradrenergic transmission. At the same time, we note guanfatsina greater selectivity for the alpha2-adrenergic receptor than clonidine. Withdrawal symptoms due not only to the central mechanism for strengthening the metabolism of dopaminergic and noradrenergic neurons. The normal adrenal synthesis of enkephalins and noradrenaline comes from a predecessor. In the bloodstream enkephalins and noradrenaline allocated in equimolar concentrations. Because exogenous opiate substitution own enkephalins, through a feedback mechanism, there is inhibition of the synthesis of the past, switching to the path of increased synthesis of norepinephrine [2]. Thus, despite the fact that the trigger withdrawal symptoms in displacement of the drug from the opiate receptor is to increase dopaminergic transmission in the reward-system, leading role in behavioral and autonomic symptoms in playing "noradrenergic storm". The first step in any treatment program is a seizure of drug addiction and the relief of withdrawal symptoms. Even the most effective methods of relief of opiate withdrawal syndrome with the use of large doses of atropine, clonidine, pirroksan, butiroksana, painkillers, tranquilizers and certain neuroleptics, antidepressants suggest eliminating most painful withdrawal symptoms for a long period. The smallest duration of withdrawal syndrome (5 to 7 days) indicated in arresting the latter using normal dose (50 mg daily) naltrexone. Some of the patients in this connection rejects these therapies, demanding the immediate removal of painful experiences by any means. Pathophysiologically all detoxification methods, recommended and officially sanctioned NIDA, can be divided into three major groups: 1) based on the replacement of detoxification of heroin and other opioids more manageable mu agonists (methadone, etc..) To progressively reduce the dosage to the complete abolition of the latter; 2) based on the displacement detoxification heroin and other opioid agonists / antagonists (buprenorphine, LAAM, et al.), And then cancel the agonist-antagonist; 3) detoxification through the displacement of heroin and other opioid antagonists (naltrexone, naloxone, nalmefin). The faster detoxify (ie, the displacement of heroin and / or other opiates opioid receptor), the more pronounced withdrawal symptoms. The most rapid detoxification methods belong to the third group - based detoxification of opioid antagonists. This is a classic method of detoxification, which naltrexone applied in progressively increasing doses with concurrent reduction of the dose of heroin. Naltrexone treatment start with a daily dose of 10 mg and gradually adjusting for 5-7 days daily dose of 50 mg. During this time, reduce and totally cancel the drug. Relief of withdrawal symptoms is achieved in 5-7 days, but quite pronounced withdrawal symptoms while preserving both mental and autonomic components. This significantly reduces the efficiency of this method, because of the interruption of patient detoxification [4,14,18]. The method of ultra-opioid detoxification (AMLO) (ultra rapid opioid detoxification) under general anesthesia was adopted in the late 80s. Today, this method is widely used throughout the world as the initial stage of the program of treatment and rehabilitation of patients with heroin addiction, but published data on clinical experience with AMLO extremely small. In contrast to the classical methods of detoxification, UROD begin with large doses of antagonists (10-12.5 mg naloxone, naltrexone 150-200 mg), using the principle of satiation (once, fractionally, or within the first hour procedures). This allows you to displace the heroin from the largest possible number of opioid receptors, which guarantees the reliability of AMLO as a method of detoxification [19]. Heroin and / or other opioid cancel prior to the procedure. Such intense "washing out" of exogenous opiates from the central nervous system and the body as a whole, with the replacement of the opioid receptor antagonist leads to the development of withdrawal symptoms expressed. The intensity and severity of withdrawal symptoms requires a very profound inhibition of the central nervous system, which is only possible with a deep level of anesthesia. Clinical experience shows that the peak of abstinence syndrome lasts for 2-3 hours after the saturation of the patient's antagonists. This period of time the patient is under anesthesia and not experiencing painful withdrawal symptoms. Vegetative component withdrawal syndrome suppressed an adequate level of anesthesia and drugs that are used in the preparation of the patient during sedation. General anesthesia usually lasts from 4 to 6 hours. Such vegetative reactions like bronhoreya, vomiting, increased secretion of gastric contents require maximum protection of the upper respiratory tract. Therefore, to date, all the researchers came to the conclusion that the need for endotracheal anesthesia with controlled mechanical ventilation [8]. After awakening and extubation may experience residual effects of withdrawal symptoms, which not only enhanced, but quickly regress. If necessary, patients receive additional medication to alleviate some residual symptoms of withdrawal syndrome. Trying to eliminate the patient's past drug use will not cause a euphoria. This is due to the use of the procedure UROD long acting opioid antagonist naltrexone is present in the body for several days. Another advantage of the described method is the possibility to start naltrexone maintenance therapy at a daily dose of 50 mg immediately after awakening and extubation of the patient [4]. Thus, the principal features of the method AMLO are: 1. The use of high doses of drugs that block opiate receptors (naloxone, naltrexone). 2. The absence of painful sensations characteristic of opioid withdrawal, as the patient for hours under general anesthesia. 3. The duration of the detoxification is 4-6 hours. According to the literature, methodology AMLO largely reflected the evolution of the method than the differences and peculiarities. Publications before 1994 [10,11] reported an AMLO under midazolam sedation without intubation. At the same time, despite the use of high doses of midazolam 0.5-0.7 mg / kg of naltrexone daily dose of 200 mg during the procedure were observed agitation, erection, shivering. Withdrawal was investigated by scoring system, without naloxone test and determination of opiates in urine, which limited the assessment of the effectiveness of detoxification. Despite the fact that the authors point to the absence of vital violations and focus on sedation rather than general anesthesia given dose of midazolam is likely to suggest inhibition of reflexes during the procedure and unnecessary risk to patients. In the standard scheme of anesthesia (hypnotic, relaxant, ALV) used various combinations of drugs [16]. The authors believe that the barbiturates have a positive effect on the braking dopaminergic transmission mediated through GABAergic receptor complex. However, the assumption of the detoxifying effect of naloxone potentiation of barbituric acid derivatives has not been confirmed [12]. There are reports on the use of isoflurane in a closed circuit. As a short-acting drug widely received propofol [8.16]. The use of mechanical ventilation compared with spontaneous ventilation through an endotracheal tube more justified as AMLO increased minute ventilation and work of breathing. [8] In addition, increased psychomotor readiness easily controlled by the patient [8]. Because muscle relaxants commonly used atracurium and norkuron. The overwhelming majority of researchers carried out the procedure under the AMLO endotracheal anesthesia and using large doses of naloxone and naltrexone. The authors note the stable during anesthesia, but without any additional medication (clonidine, odansetron, ranitidine) vegetative withdrawal syndrome component remains quite pronounced [10,19]. UROD carried out in the following embodiments. After induction of anesthesia and intubation during the first hours of the procedure is quick saturation of the patient naloxone to 12.4 mg, starting with 0.4 mg [9], or 10 mg administered bolus [11,12,15]. 1 hour before the closure procedure nasogastric naltrexone is administered at a dose of 50 mg naloxone infusion and continued for 24 hours at a dose of 0.4 mg / hr. If naltrexone in the first day is not used, or used within 12 hours after the first dose of naloxone, the naloxone dose is doubled - 0.8 mg / h [13]. Vegetative withdrawal symptoms such as bronhoreya, increased production of gastric contents, vomiting, increased salivation require inclusion of premedication and application during the procedure of additional drugs. In order to reduce gastric secretion premedication added histamine receptor blockers (ranitidine). The biggest problem is profuse diarrhea, which is not suppressed by anesthesia. The most effective drug is octreotide (odansetron) - analogue of the growth hormone that significantly inhibits diarrhea [10]. Almost all the authors note a moderate hyperdynamia circulation, mainly due to an increase in stroke volume. Total peripheral resistance substantially the same [9]. During the procedure UROD plasma epinephrine levels increased 30 times and 3 times noradrenaline. Therefore, the first day after UROD recommend the use of clonidine at a dose of 2 mg / kg / h [9]. The clinical effectiveness of the procedure AMLO evaluated on a points test (Wang, Kolb, Bradley). An objective assessment methodology - naloxone test - is used in case of doubt, the application of low doses of naloxone (2 mg) in a scheme of detoxification. Detoxification is considered complete after the disappearance of opioids (heroin, morphine, methadone) in the urine. Reports of deaths in AMLO absent. The method of regression calculated that the probability of fatal complications of AMLO under endotracheal anesthesia may be 1 to 15,000. According to NIDA, when AMLO number of positive outcomes (remission lasting at least 6 months) is 70-90%. The effectiveness of traditional treatments is estimated as 20-30%. Especially it should be emphasized that, unlike all existing techniques UROD opioid detoxification efficiency does not depend on the sex, age, and most importantly, the duration of addiction and drug daily dose of the drug. AMLO is a method of removing the drug and not the treatment of heroin (opioid) addiction. But in the treatment of addiction is the most difficult patient withdrawal from the drug, and it is associated with this stage so the low efficiency of the treatment in other programs. Postdetoksikatsionnaya therapy is generally accepted within the complex rehabilitation programs for drug addicts. Naltrexone lasts up to 6 months in different circuits. Schemes of naltrexone is selected for the clinic, depending on the mode of social adaptation and participation in psychotherapeutic rehabilitation programs. Ultrafast opioid detoxification
AV Butrov, SG Tsimbalov Department of Anesthesiology and Intensive Care Moscow People's Friendship University Treatment of heroin or methadone addiction, withdrawal withdrawal, detox, Detoxification, AMLO, Naltrexone implants. For the people of Europe the price of treatment - 600 euro: detox from heroin to 3 days (full, painless cure of the drug), accommodation, food + meeting, transfer to hotel (shuttle). TSIPO "MOSMEDSERVIS" - Russia - Moscow Tel: + 7 495 782 78 12 or Email: mosmedservice@yandex.ru Clinic Medical Center of family psychology and Addiction Ambulance Diagnostic Equipment Inform Medical Systems | |
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