IX Symposium of Macedonian association of toxicologists by Niko Bekjarovski

IX Symposium of ZTM with international participation IX Симпозиум на Здружението на токсиколози на Македонија со меѓународно учество IX Symposium of the Macedonian Association of Toxicologists with International participation

Kniga so prezentacii

Book with presentations

Centre for education ALKALOID Dojran, 18-20 November 2011

IX Symposium of ZTM with international participation

Organizing committee of the Symposium      

Nestor Popovski Niko Bekjarovski Zhanina Pereska Natasha Simonovska Irena Jurukov Isa Mucha

Symposium is accredited by the Medical Chamber of Macedonia (LKM) and the Macedonian Medical Association (MLD)

GENERAL SPONSOR OF THE SYMPOSIUM AD Alkaloid Skopje

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

Macedonian guidance for the Use of Lipid Resuscitation Therapy in acute poisonings Niko Bekjarovski, Irena Jurukov, Aleksandra Babulovska, Fani Lichoska University Clinic for Toxicology Skopje, Macedonia Abstract: LipidRescue resuscitation refers to the use of an intravascular infusion of a lipid emulsion to treat severe, systemic drug toxicity or poisoning. In the last four-five years, LipidRescue has been proposed as a treatment modality for poisoning or overdose by lipophilic agents in general. Aim of the study is to present interim guidance for the use of intralipid emulsion as an antidote in acute poisonings in the Republic of Macedonia. Our guidance is based upon the ones posted on the LipidRescue.org, the UK Resuscitation Council, the Association of Anaesthetists of Great Britain and Ireland and American College of Medical Toxicology. Key words: LRT, guidance, poisosnings Introduction: LipidRescue resuscitation refers to the use of an intravascular infusion of a lipid emulsion to treat severe, systemic drug toxicity or poisoning. It was originally developed to treat local anesthetic toxicity, a potentially fatal complication of regional anesthesia that can also occur in other situations where patients receive local anesthetic injections. In the last four-five years, LipidRescue has been proposed as a treatment modality for poisoning or overdose by lipophilic agents in general. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. The first effectiveness of lipid emulsion in resuscitation from local anaesthetic overdose appeared in 1998, reporting its successful use in rats [1]. A similar paper reporting successful results in dogs appeared in 2003 [2]. This was followed in 2004 by publication of a suggested treatment regimen for local anaesthetic-induced cardiac arrest in humans using lipid emulsion, dubbed „lipid rescue‟ [3]. An editorial in “Anesthesia” journal in 2006 highlighted its probable efficacy in humans and pointed out that ethically acceptable, randomised, controlled trials of lipid rescue in humans would be impossible [4]. In the same year, the first peer-reviewed accounts of lipid rescue‟s effectiveness in local anaesthetic-induced cardiac arrest in humans appeared [5, 6]. In each of the two cases, administration of lipid rescue was associated with restoration of effective cardiac output. The first systematic review of effectiveness of lipid emulsion in treatment of acute poisonings was published in Clinical Toxicology on January 2010 [7]. All analyzed case and human trials (less than 50) suggest some benefits of lipid emulsion in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity, but without any trial that assessed the safety of Lipid emulsion in the treatment of acute poisoning. Ten months later the range of effectiveness was extended with cases of acute poisoning with parasiticides, herbicides and several varieties of psychotropic agents [8]. Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

In April 2011, Journal of Emergency Medicine Australasia published the summary study of all acute poisonings treated with intralipid emulsion (ILE). Forty-two cases of ILE use (19 local-anaesthetic, 23 non-local-anaesthetic) were identified, with anecdotal reports of successful resuscitation from cardiovascular collapse and central nervous system depression associated with ILE administration in lipophilic toxin overdose. Although significant heterogeneity was observed in both agents of intoxication, and reported outcomes; case report data suggest a possible benefit of ILE in potentially life-threatening cardio-toxicity from bupivacaine, mepivacaine, ropivacaine, haloperidol, tricyclic antidepressants, lipophilic beta blockers and calcium channel blockers [9]. Aim of the study is to present interim guidance for the use of intralipid emulsion as an antidote in acute poisonings in the Republic of Macedonia. Our guidance is based upon the ones posted on the LipidRescue.org [10], the UK Resuscitation Council [11], the Association of Anaesthetists of Great Britain and Ireland [12] and American College of Medical Toxicology [13]. INTERIM GUIDANCE FOR USE OF LIPID RESCUE THERAPY IN MACEDONIA  Use of LRT is to be based on the clinical judgment of the treating physician.  Use of LRT could be helpful in severe poisonings with local anesthetics, poisonings with Ca antagonist, β blockers, tricycles antidepresives and other lipophilic drugs and substances.  Think for LRT if one of these signs are noted:  Cardiovascular collapse: sinus bradycardia, conduction blocks, asystole and ventricular tachyarrhythmias  Cardiac arrest  Sudden loss of consciousness, with or without tonic-clonic convulsions (GCS < 6) Protocol for treatment Give an intravenous bolus injection of Intralipid®/Lipofundin® 20% for 1 min o Give a bolus of 60-120 ml ( 60 ml for patients with < 30kg, 80 ml patients between 3060kg, 100ml for patients between 60-90kg and 120 ml for patients over 90kg.) Use syringes of 50 or 20 ml. • Continue CPR • Start the rest of Intralipid®/Lipofundin® (380-440ml). o Give at a rate of 400 ml over 20 min • Repeat the bolus injection twice at 5 min intervals if an adequate circulation has not been restored o Give two further boluses of 100 ml at 5 min intervals o Give the rest of 20% lipid infusion over 10 min References: 1. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine induced asystole in rats. Anesthesiology 1998; 88: 1071–5.

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

2. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Regional Anesthesia and Pain Medicine 2003; 28: 198–202. 3. Weinberg G. Reply to Drs Goor, Groban and Butterworthlipid rescue:caveats and recommendations for the „„Silver Bullet‟‟. Regional Anesthesia and Pain Medicine 2004; 29: 74–5. 4. Picard J, Meek T. Lipid emulsion to treat overdose oflocal anaesthetic: the gift of the glob. Anaesthesia 2006; 61:107–9. 5. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia 2006; 61: 800–1. 6. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacainerelated cardiac arrest. Anesthesiology 2006; 105: 217–8. 7. Jamaty C, Bailey B, Larocque A, Notebaert E, Sanogo K, Chauny JM.Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies. Clin Toxicol (Phila). 2010 Jan;48(1):1-27. 8. Rothschild L, Bern S, Oswald S, Weinberg G.Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010 Oct 5;18:51. 9. Cave G, Harvey M, Graudins A. Intravenous lipid emulsion as antidote: a summary of published human experience. Emerg Med Australas. 2011 Apr;23(2):123-41 10. Weinberg G (2007) LipidRescue: resuscitation for cardiac toxicity http://www.lipidrescue.org/ 11. Resuscitation Council (UK) (2010) Resuscitation Council (UK). http://www.resus.org.uk/ 12. AAGBI (2010) The Association of Anaesthetists of Great Britain and Ireland. http://www.aagbi.org/ 13. ACMT Position Statement: Interim Guidance for the Use of Lipid Resuscitation Therapy American College of Medical Toxicology; J. Med. Toxicol. (2011) 7:81– 82

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

NOVEL RECREATIONAL DRUGS OF ABUSE – AN OVERVIEW Hultén Peter, Swedish Poisons Information Centre, Stockholm, Sweden Objective: In recent years a large number of these new synthetic psychoactive substances (»legal highs«) have appeared as alternatives to illegal drugs. These novel recreational drugs are often synthetic research chemicals or herbal materials containing psychoactive natural substances sometimes adulterated with synthetic compounds. The novel drugs of abuse are often available for purchase over the Internet and are commonly legal to use, possess, and supply. In several countries different control measures have been put into force. Some main groups are cannabinoid receptor agonists (»Spice«), piperazines, phenethylamines (including amphetamines, cathinones, ring substituted phenethylamines), tryptamines, and ketamine and phencyclidine derivatives. Discussion: The overall population prevalence of use of novel recreational drugs is difficult to assess since most reports, e.g. the UN World Drug Report and the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), do not enquire about novel compounds since the focus is on “classical” substances. The source is the drug dealers on the street market, but also the Internet and street “head shops”, particularly when the drugs first become available. These drugs are frequently sold as “bath salt”, “fertilizer”, “plant food” and/or labeled as “not for human consumption” or “research chemical” to elude the legislation. Most of these substances are produced in China or India and shipped into Europe and North America in bulk quantities where they are packaged into dose quantities before being sold to the user. The content of the products often changes, sometimes including illegal substances, leading to increased risk of toxicity and risk of criminal conviction. Over 40 new substances were reported in 2010 to the EMCDDA via the EU early-warning system. The challenges are to identify the compounds and determine their acute toxicity. To identify the acute toxicity of these compounds poisons centre data, admissions to hospital and death case statistics could be used. This information is difficult to assess and may lack analytical confirmation. Common clinical features seen in individuals include wide pupils, agitation, tachycardia, hypertension and seizures. Most poisonings are benign and symptomatic treatment is normally sufficient. Conclusion: Risks new psychoactive substances are not fully documented and serious clinical symptoms have occurred, even fatalities. Therefore it is of great importance that clinicians are informed about the risks associated with the use of novel recreational drugs. Key words: recreational drugs, abuse

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

The effects of Poisonings Information Centre‟s (PIC) activities - an Estonian example Mare Oder MSc RN Estonian Poisoning Information Centre (EPIC), Heath Board, Ministry of Social Affairs Objective: To describe the PIC´s role in a community and the effects of active poison information education on the awareness of public about PIC. Introduction: EPICs mission is to provide adequate advice quickly so as to reduce the incidence of illness, damage to health and death as a result of severe cases of poisoning. In October, 2008 EPIC‟s phone line 16662 became active on business days from 09.00– 17.00; since January 2011 24h/5. No expensive media campaign was launched. EPIC has continually two educational activities – primary(PP) and secondary prevention(SP). The goal of PP is to avoid poisonings; SP is defined as reducing morbidity and mortality by creating PIC awareness. Additionally is public´s and healthcare providers‟ education, awareness of the PIC‟s phone number associated in turn with a positive impact on call volume in PIC. Method: All calls answered in the EPIC, activities, published articles and lectures about poisonings and their prevention were analysed via a time-line from the 1st of October 2008 to the 30th of September 2011. All calls concerning general information about health, diseases and other questions were classified as general questions (GQ). Only calls concerning acute exposure to poisons were defined as poisoning questions (PQ). The annual number of calls, lectures and articles was compared. Results: In order to achieve the goal EPIC launched a presentation‟s programme about poisonings, their treatment and prevention for healthcare providers and general population as well as started participating in health promotional fair. EPIC has developed the expert-status for healthcare providers, population, media, authorities. During the analysed period in total 1620 calls were answered. The structure of the calls was as follows: 2008: 90 calls: 37 (41.1%) GQ, 53 (58.9%) PQ; 2009: 331 calls: 127 (38.4%) GQ, 204 (61.6%) PQ; 2010: 450 calls: 112 (24,9%) GQ, 338 (75,1%) PQ; 2011: 761 calls: 184(24,2%) GQ, 577(75,8%) PQ. Structure of lectures/published articles (and reflections in media publications) was as follows: 2008: 3/2 (50); 2009: 9/8 (9); 2010: 12/15 (19); 2011: 20/12 (96). A total annual number of deaths from poisoning decreased from 410 (in 2007) to 300 (in 2010). Conclusion: Active, systematic poisonings information activity, education increases the awareness, confidence of the population to the PIC and has a positive impact on the volume of poisoning calls handled by the centre. The educational programmes did not have an immediate effect but had a positive effect from a longer perspective. As earlier published articles described, combining PP and SP in one initiative may have a positive impact on PIC‟s call volume and might influence number of deaths from poisonings. Key words: role, Poisoning center, Estonia

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

NUMBER OF DEATHS BECAUSE OF ETHANOL INCREASES IN SLOVENIA Marija Jamsek, Milos Kravanja, Lucija Sarc Poison Control Centre, University Medical Centre, Ljubljana, Slovenia Introduction. Ethanol – a legal drug is the most commonly used psychoactive substance. Ethanol abuse represents a large social and health burden. Ethanol abuse causes many chronic diseases and is involved in complications by management of many other diseases due to withdrawal. There is an increase in mortality because of ethanol in Slovenia. Aim. In this study we analyse national epidemiological data about deaths caused by ethanol in the last ten years period. Methods. The epidemiological data for the dead because of ethanol in years 2000 and 2009 were obtained from The Institute for Public Health of Republic of Slovenia (IPH RS). Their national statistical data are based on “The International Statistical Classification of Diseases” (ICD-10). 25 Codes related to ethanol were divided in 5 groups: T51.0, F10.0 and F10.1 acute ethanol poisoning; F10.2, F10.3 and F10.4 ethanol withdrawal; K70.0, K70.1, K70.2, K70.3, K70.4 and K70.9 ethanol hepatopathy; I42.6 ethanol cardiomyopathy; F10.5 F10.6, F10.7, F10.8, F10.9, E24.4, E51.2, G31.2, G62.1, G72.1, K29.2 and K86.0 others. We compared the number of dead in both years in each code group in relation to gender and age group. Results. A total number of the dead in year 2000 is 475 and 840 in year 2009, what represent an increase by 77%. Gender distribution is in average in both periods similar; 75% of the total dead because of ethanol belong to males and 25% to females. In the both periods is the leading cause for the mortality of alcoholics ethanol hepatopathy, followed by ethanol withdrawal, acute ethanol poisoning and ethanol cardiomyopathy. Comparison of the code group distribution shows in year 2009 an increase of hepatopathy share by 25%, a decrease of ethanol withdrawal share and acute poisoning share by 30% and 43% respectively in comparison to year 2000. Peak of age group distribution is in an age group 50-64 years for males and in age group above 65 years for females in both periods

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Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

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(Figure1).

IX Symposium of ZTM with international participation

Conclusions. The mortality increase because of consequences of ethanol abuse almost redoubled in the last ten years. Three fourth of the dead because of ethanol belong to a male population. Leading cause of mortality among chronic alcoholics is ethanol hepatopathy for both genders. We estimate that absolute number of the deaths because of ethanol is underestimated; some deaths because of ethanol do not get one of the above mentioned codes thus they are hidden behind pneumonia, sepsis, trauma or haemorrhage. Key words: ethanol. deaths, Slovenia

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

Benzodiazepines–Drugs or poison? Irena Ignjatović, Emergency medicine ward, General Hospital in Leskovac, Serbia Introduction: In many countries around the world the most frequent case of poisoning is acute drug poisoning. Epidemiological data concerning poisoning cases in Belgrade, the capital of Serbia, for the period from 1995 until 1998 shows precisely that the most frequent and effective causers of acute poisoning with chemical substances are drugs. Among them benzodiazepine medicals (taken with or without other chemical substances) take part with 50% of all cases; moreover, benzodiazepines have become the most frequent causer of poisonings, often deliberately ones, due to their wide availability. Toxicity of benzodiazepines is very small; that is the main reason why the poisoning cases are not so severe. In the majority of cases they are combined with alcohol and opiates. Even though the clinical image has a difficult course, these poisonings can sometimes be severe if the patients who took the drugs were elderly persons or in case of so called „combined‟ poisonings. Aim of the paper: The aim of this paper is to show the frequency and modes of treating the patients with acute, benzodiazepine drug poisoning in the Emergency Room (ER) of the Hospital in Leskovac. The author‟s intention was also to show the importance and the role of an ER specialist in reception and emergency hospital treatment of the patients with acute drug poisoning. Methods: The research was conducted as a retrospective, nine-year observational study, analyzing the data from the admission and triage protocol of the department of the ER, where patients are received and treated according to the protocol for the patients with acute poisoning, as well as the data from the stationary department, the Toxicology Unit, in the period from the beginning of 2002 to the end of 2010. The method of quantitative analysis of the total number of the patients with poisoning and the number of patients with benzodiazepine drug poisoning was used, accompanied with graph, percentage and table overviews. Results: In the period from the beginning of 2002 till the end of 2010, 297 737 patients were admitted in Emergency ward, 1.08% of whom with acute poisoning, were examined in the Emergency Room of the hospital in Leskovac. The largest number poisoning is drug poisoning with 34.82%. There was an increase from 62 drug poisoning in 2002. To 216 cases in 2010. From the total number of drug poisoning, 72% of cases were intoxications with benzodiazepine drugs; poisoning cases with diazepam were observed in 43.12% of all cases. The data analysis of acutely poisoned patients showed a greater number of acute poisoning with benzodiazepines among female population (87.13%), 94.46% of which was suicidal. In the majority of cases (39.56%) the PSS level 1 poisoning were recorded. Acute poisoning of patients from the age of 30 to 40 happened in 36.98% of all poisoning cases. Conclusion: Benzodiazepines as medications of wide application area and they have a greater toxicological significance, due to the high increase of suicidal cases in Jablanica district. These drugs mainly cause light poisonings what was recorded in 45% of all admitted patients in Emergency ward of General Hospital in Leskovac. Dominate signs of poisoning were noted by examining patients central nervous system and Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

cardiovascular system. Most patients, 84% of them, after being treated in the ER, were discharged home in good general condition. During the research there were not any cases with fatal outcome. The best advice for a therapeutic protocol in benzodiazepine poisoning is the application of general measures of treatment and resuscitation according to the protocol ABC, gastric lavage and medicine coal application with infusions. Poisoning facilitations at a basic level require the application of supportive therapy, stabilization of the circulatory and respiratory function, gastrointestinal decontamination and general care of patients. In the case of serious poisoning the application of basic supportive therapy and specific therapy antidote (flumazenil which is applied intravenously at a dose of 0.3 mg at the very beginning) is required. If the desired level of awareness is not reached after 60 seconds, repeated doses to a total dose of 2 mg are applied to the patient until the waking up. In the case sleepiness the readmission of intravenous infusion of 0,1-0,4 mg/h is required. In order to prevent benzodiazepine poisoning, it is necessary to reduce the free sale of these products. Key words: BNZD, poisoning, ABC protocol

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

ACUTE SALICYLATE POISONING TREATED IN THE NATIONAL POISON CONTROL CENTRE: RETROSPECTIVE STUDY Đorđević D, Režić T, Jović-Stošić J, Bokonjić D, Kilibarda V, Vučinić S Clinic of Emergency and Clinical Toxicology, National Poison Control Centre, Military Medical Academy, Crnotravska 17, Belgrade, Serbia American Association of Poison Control Centers (AAPCT) has reported the increase of salicylate exposure in a five years period, 1998-2003, and emphasized that 12,6% of all fatal analgesics poisonings have been caused by salicylates. OBJECTIVE: The aim of this study was to analyze the frequency, the most frequent features and severity of acute salicylate poisoning treated in the National Poison Control Centre (NPCC). MATERIALS AND METHODS: The restrospective study was performed in the Clinic of Emergency and Clinical Toxicology, NPCC, Military Medical Academy, Belgrade. RESULTS: During the five years period (2005-2009), 5463 patients with acute poisoning were hospitalized and 30 (0,549%) of them had acute salicylate poisoning. Poisoning was deliberate in all the cases, and the most of the patients were women - 26 (86,6%). The severity of poisoning was determined according to the Poisoning Severity Score: 12 (40%) patients had no clinical signs of poisoning (PSS 0), but salicylates were detected in blood with the levels above the therapeutic; 13(43,3%) patients had mild poisoning (PSS 1), and in 5 (16,6%) patients the poisoning was moderate (PSS 2). The most frequent signs of poisoning were nausea, vertigo, tinnitus, epigastric pain, vomiting, somnolence, electrolyte disorders, while one patient had metabolic acidosis of moderate degree. The highest detected salicylate concentration was 520 mg/L. The therapy consisted of rehidration, correction of electrolyte disorders, H 2 antagonists or inhibitors of proton pump, and sodium bicarbonate infusion (for alkaline diuresis and correction of metabolic disorders). CONCLUSION: Acute salicylate poisoning, although not so frequent could be a clinical problem, and it is necessary to provide prompt diagnosis, supportive and symptomatic treatment. Alkaline diuresis is indicated for patients with any sign of poisoning and should not be delayed untill salicylate levels are determined. However, serum levels are helpful in confirming the diagnosis and may help guide therapy, but levels may also be misleading and should be clinically correlated. Key Words: acidosis, salicylates, poisonings

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

СТИМУЛАТИВНА (МОДЕЛ) ПСИХОЗА ВЕРСУС ШИЗОФРЕНИЈА Дарко Костовски, Оливера Суботин Психијатриска болница Скопје Психозите предизвикани од амфетамини се експериментален модел на параноидна шизофренија. Овие психоактивни супстанции употребувани како дроги се неврохемиски медијатори на ЦНС кои предизвикуваат синдром на параноидна состојба. Тоа е ткн. Модел психоза кај која се целосно изразени аудитивните и /или визуелните перцептивни измами. Овие состојби се јавуваат по интоксикација, долготрајна употреба или во рамките на апстиненцијата. Најголемиот број на истражувања на веројатните невроанатомски структури одговорни за појавата на на шизофренијата, се фокусирани на субкортикалните јадра. Постојат и докази за промени предизвикани од употребата на амфетамини и во префронталниот кортекс. Од особена важност за секојдневната клиничка пракса во психијатриските и другите медицински институции е диференцијацијата на оваа состојба во однос на параноидната шизофренија. Акцентот на овој клинички ентитет се дава поради голем број на млади лица кои употребуваат рекреативни стимулативни супстанции или во случаите на комбинирана зависност. Дополнително, лицата што користат исклучиво амфетамини, најчесто бараат медицинска помош само во случај на психотична декомпензација. Сцената на корисниците на стимулативни дроги е стабилна, но не е толку достапна за службите и невладините организации, компарирана со сцената на корисниците на опијати. Key Words: psychosis, schizophrenia, psychoactive drugs;

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

Metabolic acidosis caused by corrosive agent ingestion – main characteristics and specific therapeutic approach Režić T, Vučinić S, Babić G, Potrebić O, Đorđević D, Perković-Vukčević N, VukovićErcegović G, Bokonjić D, Jović-Stošić J Clinic of Emergency and Clinical Toxicology, National Poison Control Center (NPCC), Military Medical Academy Belgrade, Crnotravska 17, Serbia Acute poisoning with corrosive agents treated in NPCC, make 15% to 20% of all hospitalizations, and also the main cause of a fatal outcome. Metabolic acidosis is one of the most important systemic disturbance which may be caused by this kind of poisoning. OBJECTIVE: The two main goals of this study were to determine the frequency, type and severity of metabolic acidosis as well as the efficacy of sodium bicarbonate therapy during the corrosive agents poisoning. MATERIAL AND METHODS: The retrospective study included 112 patients, 83 (74%) were female, 29 (26%) male, hospitalized in our facility throughout two years period (from 2008. to 2009.). Patients were categorized by two major criteria: Poisoning severity score (PSS 1-4) and by the type of corrosive substance (six groups). Parameters of blood acid-base status are determined by the ABL 735 analyzer-Radiometer. RESULTS: Acid-base profile was determined initially in 73 out of 112 patients (65%). Metabolic acidosis (Standard Base Excess or SBE< -2,5 mmol/l) was proven in 56 samples (77% of analyzed). All of them were a high anion gap acidosis (AG>11mmol/l). In etiological group 1 (acetic acid) 32 (76%) acidosis was confirmed with an average of SBE = -10,7 mmol/l, and in group 2 (hydrochloric acid) 17 (89%) , average SBE= -12,8 mmol/l. These two groups have also shown good correlation between PSS and the severity of acidosis, with statistical importance of subgroups PSS4 (lethal poisonings) compared to groups PSS1, 2 and 3: in group 1 (p<0,001), in group 2 (p<0,05). Intoxication with sodium hydroxide (group 3) caused moderate acidosis (SBE= -6,1 mmol/l) in four cases (57%). Thirty three patients were treated with sodium bicarbonate (4,2% or 8,4% infusion), during an average period of 24 hours from time of admission. Initial mean values of blood bicarbonate concentration or cHCO 3 (16 mmol/l) and SBE (11,1mmol/l), were significantly improved at the end of the therapy (cHCO 3 22 mmol/l, SBE= -3,1 mmol/l respectively; p<0,001). CONCLUSION: initial assessment and follow up of metabolic acidosis is an obligatory diagnostic procedure to determine the severity of the poisoning, prognosis and therapeutic efficacy in cases of corrosive chemical poisoning. Key words: acidosis, corrosive ingestion,

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

PLASMAPHERESIS APPLIED AT ACUTE SUICIDAL POISONING BY CARBAMAZEPINE (EPITOL, TEGRETOL, ATRETOL) AND BENZODIAZEPINE-DIAZEPAM B.Pavlovski, A.Cibisev, G. Spasovski, V.Nikolov, N.Popovski, L.Trencevska, L. Milosevska University Clinics for Toxicology and Nephrology, Skopje, R. Macedonia Background: Clinical applications of plasmapheresis are rapidly increasing as a method of detoxification in the field of clinical toxicology. Carbamazepine in blood is 76% bound to plasma proteins. Initial half-life values range from 25-65 hours, decreasing to 12-17 hours on repeated doses. Carbamazepine is metabolized in the liver. Cytochrome P450 3A4 was identified as the major isoform responsible for the formation of carbamazepine10,11-epoxide from carbamazepine. Peak plasma levels occur 4-8hours after administration… Most of the toxicity is due to the CNS depression and anticholinergic effects. Diazepam and its metabolites are highly bound to plasma proteins (diazepam 98%). The aim of this case report was to demonstrate successfully treatment using plasmapheresis by evidence of effective clearance of remedies and change comatose status to full consciousness. The patient N.N 29 old man, prisoner, was admit at our clinic on 02.10 .2011 in the evening hours, 24 hours after suicidal ingestion of unknown remedies. He was in comatose status, with tachycardia, mydriasis, and dry mucous membranes. Following routine biochemical blood and urine tests were made: SE,ER , Hm, Pl,Le,Glicemia. Enzymatic status: ALP, AST, ALT, LDH, GGT..degradationes products: Urea, Kreatinine-serum.Total bilirubine , Dir bil,Ind bil,. .Electrolytes status: Na, Ka, Ca..Lipoproteins status: Total lipids, Trigl,Total Hol, Hol-est, HDL, LDL.Urine: PH, Prot, Glicemia, Le. ECG and blood pressure were continually monitoring, and specially QRS and QT prolongation. Toxicological substances were determined using TLC ( Thin Lower Chromatography). Using this method we detected presence of Carbamazepine and Benzodiazepines in the urine. Plasma concentration of Carbamazepine and urine concentration of Benzodiazepine we measured using Fluorescence Polarization immunoassay (FPIA) technique on Abbott TDx FLx instrument. Result: Two consecutive plasmapheresis were made. We measured the plasma concentrations of Carbamazepine before the treatment and after to the each plasmapheresis.These are plasma concentration of Carbamazepine: Before the first treatment -275mmol/L, after the first treatment-140mmol/l, after the second treatment 54mmol/L. (Ref. values 17- 50mmol/L,for the patients who take therapeutic doses of Carbamazepine.Urine concentration of BZD before the treatment were: 862,29ng/ml. Resume: We measured the plasma concentrations of Carbamazepine at this intoxication and we found clinically significant clearance with plasmapheresis. Because of a lack of large controlled series, the rationale for using plasmapheresis must be confirmed in each type of intoxication by evidence of effective clearance, as well as by high plasma protein binding and a low volume of distribution of the toxic substances. Key words: Plasmapheresis, acute suicidal poisonings, Carbamazepine, Diazepam. Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011

IX Symposium of ZTM with international participation

ALCOHOLIC CARDIOMYOPATHY in 33 year old male patient A.Stevchevska, A.Chibichev, B.Pavlovski University Clinic for Toxicology, Skopje Introduction: Alcoholic cardiomyopathy is a type of dilated cardiomyopathy which represents 3,8% of all cases of CMP in general. It is concidered that the duration of alcohol consumption(over 5 years) and the amount of daily alcohol ingestion (over 90g per day), have important role in the apeareance of the alcoholic cardiomyopathy. Case report: We present a case of 33 year old patient admited to our clinic during two weeks, in march 2009', because of dyspnea, bilateral leg swelling,progresive abdominal swelling, nausea, intense fetigue-reduced effort tolerance, especially the last two weeks before admission. The patient was without positive hystory of hospital admissions or health issues of any kind before , with anamnestic data of 1/2 litar of daily alcohol uptake last ten years. On examination the patient had bilateral basal crepitations and systolic murmur over mitral and tricuspidal valve.Also the abdomen was meteoristic with positive sign of fluctuation,congestive hepatomegaly and bilateral pitting crural oedema. During hospitalisation following examination were made: ECG; biochemical labaratory analysis, echocardyography, abdominal echosonography, chest x-ray. Since the given anamnestic information, also absence of precipitating moments in patient's hystory ,and according to the performed tests and analysis , a diagnosis of alcoholic cardiomyopathy was made. Conclusion: Long term heavy alcohol abuse is second leading cause of dilated CMP. Since there are no specific criteria for diagnosis of ACM , the key factor in rulling is long term hystory of alcohol consumption. It has been shown that alcohol abstinence besides hearth failer therapy is nessecery in the treatment of this patients. Key words: alcohol abuse, dilated cardiomyopathy, echocardiography

Центар за едукација АЛКАЛОИД ДОЈРАН 18-20 Ноември 2011