Search

3,4-Methylenedioxymethamphetamine (MDMA) remains one of the most commonly used recreational drugs in Europe. Monitoring of Emergency Department (ED) presentations with acute toxicity associated with MDMA is important to determine trends in MDMA use and harms. Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all ED presentations with acute toxicity involving MDMA use, alone or in combination with other substances, between 1 January 2014 and 31 December 2017. Geographical distribution, time trends, patient demographics, clinical features, management and outcome were analysed. Out of 23,947 presentations, 2013 (8.4%) involved MDMA, used alone (88, 4.4%) or with other substances (1925, 95.6%). The proportion of MDMA presentations varied by country, from over 15% in France to less than 5% in Norway. For the 15 sentinel centres where data were available for all four years, MDMA-related presentations peaked in 2016 (10.4% versus 8.1% in 2015, p p = 0.0002). 1436 (71.3%) presentations involved males. Females were significantly younger than males (median 23 years, interquartile range, IQR, 20–27 years, versus median 25 years, IQR 21–30 years, p versus 43.9%, p = 0.02), were more frequently medically discharged directly from the ED (74.7% versus 62.4%, p = 0.03), and less frequently received sedation (43.5% versus 66.5%, p = 0.003). This large multicentre series of MDMA presentations to EDs showed geographical variation and changes in time trends and in patient demographics. Triangulation with data from complementary sources including seizures, prevalence of use and wastewater analysis, will enable a greater understanding of the public health implications of MDMA use in Europe.

International audience; Following the development of the tramadol crisis currently affecting countries in the Middle East, and Africa, there has been increasing international interest in the regulation of tramadol. This study investigates the misuse of tramadol in patients presenting to emergency departments across Europe. Data from 32 emergency departments in 21 countries were extracted from the Euro-DEN Plus database for the 4-year period from 1 January 2014 to 31 December 2017. Of the reported 24,957 emergency department presentations, tramadol misuse was reported in 105 (0.4% presentations). Tramadol misuse was most common in Bratislava (Slovakia; n = 11, 7.5% of all presentations to this centre), Riga (Latvia; n = 4, 4.9%) and Munich (Germany; n = 17, 2.9%). On arrival, 14 (13.3%) of presentations were in coma/Glasgow coma score ≤ 8 and 9 of these had a respiratory rate

Objective: Due to shortage in Zagreb antivenom availability, in Slovenia V. ammodytes bites have been treated with French and UK antivenoms in the recent years. In Croatia, for therapeutic purposes the remaining doses of Zagreb antivenom have still been used. Composition differences between these three antivenoms exist. First, they differ in specificity. Zagreb antivenom (Croatia) is raised against V. ammodytes venom, but is clinically effective and used against all European venomous snakes. Viperfav (France) is raised against the mixture of V. aspis, V. berus and V. ammodytes venoms, but was mostly used against V. aspis and V. berus. ViperaTAb (UK) is raised against V. berus venom solely, and used so far only to treat envenomations caused by V. berus until recently. Second, they differ in type of the active drug component, since Zagreb antivenom and Viperfav are F(ab')2-based, while ViperaTAb is Fab-based preparation. And third, investigated antivenoms have differently prescribed administration routes - intravenous for ViperaTAb and Viperfav or intramuscular for Zagreb antivenom. Aim was to reveal pharmacokinetic profiles of currently available antivenoms in V. ammodytes envenomations and their influence on venom level decrement. Methods: The study represents prospective case series of consecutive patients envenomed by V. ammodytes snakebite and mostly treated with Zagreb antivenom or ViperaTAb in University Hospital of Split or Ljubljana since 2015. In serum samples concentrations of F(ab’)2 or Fab fragments, venom and neurotoxic ammodytoxins were determined. Pharmacokinetic parameters of antivenoms were evaluated whenever possible. Results: Nine patients were treated with Zagreb antivenom and six with ViperaTAb, one of which received Viperfav also. Pharmacokinetic profile differences were revealed. Systemic clearance of ViperaTAb was between 4.3 and 23.2 (mL h-1) / kg. Its distribution and elimination half- lives were in range of 0.4-3.2 h and 12.9-55.9 h, respectively. In the case of Zagreb antivenom, due to prolonged residence time, even the sampling period of 96 h post-treatment was not sufficient for estimation of pharmacokinetic parameters. The exception was 8 days hospitalized patient, revealing systemic clearance of 0.42 (mL h-1) / kg and half-life of 317.2 h. Venom was detected in serum of all patients, in contrary to ammodytoxins. Measured concentrations correlated with the F(ab')2/Fab level, revealing inverse trend in venom- antivenom circulation behavior. Conclusion: Antivenom level was highly dependent on the fabotherapics type and administration route, significantly affecting reappereance and systemic clearance of V. ammodytes venom and its neurotoxic component as well.

The study was a prospective multicentre survey of Viperidae snakebites and use of antivenoms in poison control centres and toxicology departments in Estonia, Lithuania, Poland, Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Macedonia and Bulgaria. The incidence of Viperidae snakebites in central and south-eastern Europe is at least 2.9/million populations ; but is likely more, since not all snakebites would have been treated in toxicology departments or reported to local poison control centers. V. berus bites were most common, and although V. ammodytes bites had a higher median severity score it was not significant (2 compared to 1 for V. berus bites ; p = 0.18). Antivenom was used in half of the reported V. ammodytes bites (compared to 13% of V. berus bites). Three different antiViperidae antivenoms were used, none of which is European Medicines Agency (EMA)- approved. Only ViperaTab was used in both V. berus and V. ammodytes bites.

Due to current shortage in Zagreb antivenom availability, in Slovenia V. ammodytes venomous bites have recently been treated with antivenoms of French and UK producers. In Croatia, for therapeutic purposes the remaining doses of Zagreb antivenom have still been used. Composition differences between these three antivenoms exist. First, they differ slightly in specificity. Zagreb antivenom has been raised against V. a. ammodytes venom, but is clinically effective and used against all European venomous snakes (V. ammodytes, V. berus, V. aspis, V. lebetina and V. xanthina). Viperfav from the French producer has been raised against the mixture of V. aspis, V. berus and V. ammodytes venoms, but was mostly used against V. aspis and V. berus. ViperaTAb from the UK has been raised against V. berus venom solely, and used so far only to treat envenomations caused by V. berus. Second, they differ in type of the active drug component. Namely, Zagreb antivenom and Viperfav are F(ab')2-based preparations, while ViperaTAb is formulated of Fab fragments. And third, investigated antivenoms have differently prescribed administration routes - intravenous for ViperaTAb and Viperfav or intramuscular for Zagreb antivenom. Since ViperaTAb’s and Viperfav’s therapeutical suitability for use against V. ammodytes venom-induced toxicity lately has been reported as poorer in comparison to that of Zagreb antivenom, we aimed for elucidation of their distinct clinical efficiency. In serum samples of V. ammodytes-envenomed and treated patients, collected during the few days long hospitalization, concentrations of venom, neurotoxic ammodytoxins and F(ab’)2 or Fab fragments were determined. Differences in pharmokinetic profiles of investigated antivenoms were revealed. Antivenom level in circulation was highly dependent on the active principle type and route of administration, significantly affecting venom systemic clearance and consequently, clinical status of the patient. Overall, the treatment of patients with Zagreb antivenom did not required additional doses, in contrast to particularly ViperaTAb treatment. This effect might be due to higher specificity of Zagreb antivenom for V. ammodytes venom, but also due to differences in administration route and antivenom pharmacokinetics.

Objective: Clinically Vipera berus and Vipera ammodytes envenomation are difficult to differentiate. In the past this was not a concern, but due to the current shortage in European viper venom antiserum availability, V. ammodytes venomous bites have recently been treated with ViperfavTM and ViperaTAb®. Viperfav contains polyvalent equine F(ab')2 fragments as an active principle against V. aspis, V. berus and V. ammodytes, while ViperaTAb contains monospecific ovine Fab fragments against V. berus. ViperaTAb’s and Viperfav’s therapeutic convenience for use against V. ammodytes venom- induced toxicity in humans has not been described, although protective efficacy has been proved preclinically. The aim of this study was to evaluate Viperfav and ViperaTAb in V. ammodytes envenomations. Methods: A prospective case series of consecutive patients envenomed by V. ammodytes treated with Viperfav and/or ViperaTAb in the University Medical Centre Ljubljana in 2015 and 2016. V. ammodytes venom, neurotoxic ammodytoxins, and F(ab')2 and/or Fab fragments concentrations were determined in serum samples with a pharmacokinetic analysis of the antivenoms. Results: Ten patients bitten by V. ammodytes were treated using Viperfav and/or ViperaTAb ; 5 received Viperfav, 4 ViperaTAb, and 1 patient received both. V. ammodytes venom and antivenom concentrations were measured in 5 patients. V. ammodytes venom was detected in serum of all 5 patients, but ammodytoxins were detected in only the most severely envenomed patient who developed neurological symptoms. Viperfav (4 mL) promptly reduced local swelling and improved systemic pathological signs, except recurrent thrombocytopenia. ViperaTAb (8 mL) reduced moderate swelling and temporarily improved systemic effects as well. However, this dose of ViperaTAb had no effect on neurological signs. ViperaTAb and Viperfav administration induced a decrease in V. ammodytes venom serum concentrations, but only Viperfav affected the serum ammodytoxins concentration. Viperfav’s systemic clearance and elimination half-life were 1.64 (mL/h)/kg and 97 hours, while ViperaTAb’s were 4.3–13.4 (mL/h)/kg and 14.1– 55.4 hours, respectively. Conclusion: In patients bitten by V. ammodytes, both Viperfav and ViperaTAb reduce local swelling and temporarily improve systemic effects. ViperaTAb did not affect neurological symptoms or the serum concentration of neurotoxic ammodytoxins. The recommended dose of Viperfav and ViperaTAb may be inadequate in serious cases of V. ammodytes bites, therefore duplication and repetition of the treatment, with an adjustment of administration timing, should be considered. However, it should be pointed out that this study was the result of V. ammodytes antivenom shortage and it emphasises the importance of the specific antivenom availability.

depression. The aim of this study was to evaluate the clinical presentation and treatment in patients admitted to the University Medical Centre Ljubljana (UMCL). Methods: In this study we included all retrospectively reviewed cases of GHB-poisoning admitted to the UMCL between 2000 and 2014. We collected all data regarding the overdose circumstances, clinical presentation, treatment and toxicological analysis of blood and urine. Results: In the previous 15 years a total of 74 patients were admitted to the UMCL due to GHBpoisoning. The first case of GHB-poisoning was observed in 2002 and the numbers have largely increased since 2012. 86 % of all the patients ingested the drug intentionally, 82 % were male and the median age of admitted patients was 27 years. We recorded 6 mass GHB-poisonings in which 2%4 patients were admitted simultaneously. The most common presenting symptom of GHB-poisoning was a diminished level of consciousness (95 %), with 53 % being unresponsive to pain. Vomiting (30 %), bradycardia (28 %), hypotension (26 %), hypoventilation with respiratory insufficiency (19 %) and agitation upon awakening (31 %) were common as well. Concomitant alcohol and illicit drug use was recorded in 61 % of cases. 80 % of all the patients were treated symptomatically, 14 % were mechanically ventilated. Conclusions: The number of GHB-poisoned patients admitted to UMCL has increased in recent years. GHB-poisoned patients are predominantly male, often admitted in groups, who ingest the drug intentionally at parties during weekends. The most common presenting symptom of GHBpoisoning is unconsciousness. Treatment is symptomatic.

In the southeastern parts of Europe Vipera a. ammodytes and Vipera berus are the only medically important poisonous snakes. Differentiation of their bites based on clinical presentation is very difficult and unreliable. In the past this was not a concern, since snakebites were successfully treated with Viperfav™ (Aventis Pasteur, France) or European viper venom antiserum (Zagreb antivenom) (Institute of Immunology, Croatia) as formulations containing equine F(ab’)2 fragments that are either specific for both venoms, either clinically proved to be safe and effective for the treatment of V. a. ammodytes and V. berus envenomings. However, due to current shortage in ViperfavTM and Zagreb antivenom availability, V. a. ammodytes and V. berus bites have recently been treated with ViperaTAb® (MicroPharm Limited, United Kingdom) composed of ovine Fab fragments as active principle against the venom of V. berus only. Its therapeutical convenience for use against V. a. ammodytes venom-induced toxicity in human has not been described yet, although neutralisation efficacy has been proved preclinically. In view of this for the first time we present cases of several V. a. ammodytes snakebites treated with ViperaTAb® whose pharmacokinetics has been measured and correlated with clinical picture.

Paracetamol overdose results in an accumulation of the reactive, hepatotoxic metabolite N-acetyl-p-benzoquinoneimin (NAPKQI) which can cause serious liver injury. Recognition of paracetamol overdose, hepatotoxicity risk estimation and early treatment are crutial in paracetamol poisoniong management. In ingestion of potential hepatotoxic dose of paracetamol decontamination and early treatment with N-acetylcysteine (NAC) are indicated. Both, 20-hours intravenous and 72-hurs oral regimes of NAC administration are successful. By antidote regime selection we should consider patient condition and time after paracetamol overdose. In severe hepatotoxicity, criteria for liver transplantation should be regularly evaluated and mechanisms for liver transplantation must be activated in time.

Carbon monoxide is the leading cause of unintentional poisoning-related death in Slovenia. It is an odorless, colorless gas that usually remains undetectable until exposures result in injury or death. Exposure to carbon monoxide is most commonly accompanied by headache, nausea, vomiting, dizziness, confusion, drowsiness, fatigue and collapse. Carbon monoxide poisoning management includes normobaric oxygen therapy. Hyperbaric-oxygen treatments reduce the risk of cognitive sequelae after carbon monoxide poisoning.

In addition to symptomatic and supportive treatment, decontamination of the digestive tract is frequently the only therapeutic measure in the case of poison ingestion. Decontamination of the skin and eyes can also be performed, and if corrosive substances are ingested, dilution may be attempted. Decontamination methods for the digestive tract include: induction of vomiting, gastric lavage, administration of activated charcoal, intestinal lavage, forced diarrhea as well as high enema, gastroscopy and gastrotomy. Generally, decontamination of the digestive tract is most effective during thefirst hour after poison ingestion. Elimination methods are used to promote the poison's excretion from the body following its absorption. Elimination of poisons is also accelerated by administering repeated doses of activated charcoal, forced diuresis, alkalinisation and acidification of urine and extracorporeal techniques (peritoneal dialysis, hemodialysis, hemoperfusion, hemofiltration, plasmapheresis) and exchange transfusion. The decision on the need for and method of decontamination or poison elimination should be based on prior assessment of the severity of poisoning and time of poisoning, as well as the assessment of the poison's dangerousness in cooperation with the Centre for Intoxications, and the possibility of safe performance of procedures. No method should be used routinely without taking into account itsindications, contraindications and possible complications.

Eight different species of non-venomous snakes of the Colubridae family, and three different species of poisonous snakes of the Viperidae family are native in Slovenia. In the period between 1999 and October of 2008, 39 snake bites were reported to the Poison Control Centre. The most common clinical findings in snake bite victims are discernible fang marks, rapidly progressive swelling, pain, ecchymosis, lymphangitis, and regional lymphadenitis. Systemic signs of envenomation can be delayed and include gastrointestinal symptoms, hypotension, shock, respiratory distress, as well as other cardiovascular, respiratory and neurologic symptoms and signs. First aid treatment involves immobilization of the limb, reassurance and rapid transportation to a health care facility. Good symptomatic and supportive care represents the mainstay oftreatment of snake bite victims. Use of antivenom (e.g. Viper venom antiserum, European (equine)) is indicated in the case of severe local and pronounced or prolonged systemic signs of poisoning. V Sloveniji živi osem vrst nestrupenih kač iz družine gožev (lat. Colubridae) in tri avtohtone vrste strupenih kač iz družine gadov (lat. Viperidae). Po podatkih iz Registra posvetov Centra za zastrupitve je bilo v Sloveniji v letih od 1999 do oktobra 2008 zabeleženih skupno 39 ugrizov kač. Najpogostejši lokalni znaki zastrupitve po ugrizu kač so ugrizna rana, hitro napredujoča oteklina, bolečina, podplutba, limfangiitis in področni limfadenitis. Sistemska prizadetost se lahko pokaže z zakasnitvijo, najpogosteje kot prebavne težave in padec krvnega tlaka, šok, dihalna stiska ter moteno delovanje srca in obtočil, dihal in živčevja. Prva pomoč po ugrizu strupenih kač je omejena na imobilizacijo prizadetega, pomiritev bolnika in hiter transport v zdravstveno ustanovo. Bolnike po ugrizu strupene kače zdravimo simptomatsko in podporno. Indikacije za uporabo protiseruma (t. j. Viper venom antiserum, European (equine)) so hudi lokalni ali izraziti sistemski znaki zastrupitve.

The article deals with the pharmacodynamics, pharmacokinetics, clinical presentation, diagnosis and treatment of selected groups of psychotropic drugs, namely benzodiazepines, monoamin oxidase inhibitors, cyclic antidepressants and second generation serotonergic antidepressants. Epidemiologically speaking, poisonings with benzodiazepines are the commonest type of poisoning among the aforementioned groups in Slovenia. The clinical presentation of benzodiazepine poisoning is usually dominated by a decreased level of consciousness, without cardiovascular or respiratory depression. Poisonings with monoamin oxidase inhibitors show distinct characteristics of adrenergic toxidrome, and the serotonin syndrome is also a possible entity. Poisonings with cyclic antidepressants are the most dramatic from this group of drugs; they present as a combination of anticholinergic toxidrome, cardiovascular depression and/or convulsions. In recent years, poisonings withserotonergic antidepressants are becoming more common epidemiologicallv, with a somewhat less dramatic clinical presentation consisting mainly of central nervous system depression, while respiratory depression is present very rarely. Treatment of poisoning is mainly symptomatic; a specific antidotecan be administered only in benzodiazepine poisoning.