Viper envenomation in Central and Southeastern Europe: a multicentre study.

INTRODUCTION: Snakebite incidence varies across Europe. However, there is limited research from Central and Southeastern Europe. These regions are notable for the presence of the common European adder (Vipera berus) and the more venomous nose-horned viper (Vipera ammodytes). No standard European antivenom protocol exists. The aim was to assess the epidemiology and treatment of viper bites in this region, focusing on a comparison of bites from Vipera berus and Vipera ammodytes. METHODS: We conducted a prospective multicenter study in Central and Southeastern Europe from 2018 to 2020. This study included poison centres and toxicology-associated hospital wards in Poland, the Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, and Bulgaria. The following data were collected: age, gender, Vipera species, snakebite site, clinical picture, laboratory results, Audebert's clinical severity grading score, and antivenom therapy. RESULTS: The annual incidence of viper bites in Central and Southeast Europe was estimated at 2.55 bites per million population. Within their respective geographical distribution areas, the incidence of Vipera ammodytes bites (1.61 bites per million population) was higher than Vipera berus bites (1.00 bites per million population). Patients bitten by Vipera ammodytes more frequently reported local pain and developed thrombocytopenia. Antivenom treatment was more commonly administered in Vipera ammodytes bites (72%) compared to Vipera berus bites (39%). The incidence of Vipera ammodytes bites treated with antivenom within its geographical distribution area was three times higher than Vipera berus bites treated with antivenom (1.16 bites per million population versus 0.39 bites per million population). No deaths were reported. CONCLUSIONS: The estimated incidence of viper bites in Central and Southeastern Europe is at least 2.55 per million population. Vipera ammodytes bites are more common and severe, characterized by higher frequencies of pain and thrombocytopenia. Antivenom is needed more often for Vipera ammodytes bites. It is vital that enough European Medicines Agency-approved Vipera ammodytes antivenom is produced and offered affordably.

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients.

Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab')2 fragments (European viper venom antiserum, also called "Zagreb" antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab')2 fragments that were given intramuscularly only on admission. F(ab')2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab')2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.

Accidental poisoning with autumn crocus (Colchicum autumnale): a case series.

INTRODUCTION: Colchicum autumnale (autumn crocus) is a plant that contains highly toxic alkaloid colchicine. The aim was to evaluate accidental C autumnale poisoning and assess serum troponin as a prognostic parameter. METHODS: In this study, we retrospectively included all adult patients with a history of accidental C autumnale ingestion and serum colchicine confirmation during the study period from 2000 to 2019. The medical files of enrolled patients were reviewed. Literature search of accidental ingestions of C autumnale was done. RESULTS: Over the study period of 20 years, 16 adult patients were admitted to the University Medical Centre Ljubljana due to acute colchicine poisoning after ingestion of C autumnale. They all mistakenly ingested C autumnale's leaves instead of Allium ursinum in the spring and had confirmed colchicine in serum by GC-MS or LC-MS/MS (15.5 µg/L (0.5-80 µg/L)). They developed vomiting and diarrhoea within 1-9 h after the meal. Vomiting within 2 h was associated with lethality (p=.04). Bone marrow suppression developed in 15 patients (94%). Acute myocardial injury with positive troponin I (>0.10 µg/L) developed in five patients; lethal cardiogenic shock with decreased cardiac output and hypotension occurred in four of these patients despite supportive therapy. Positive troponin I ultra (>0.10 µg/L) was associated with need for intensive support therapy (p=.01), decreased cardiac output (p=.01) and death (p=.01). The mortality was 4/16 (25%). On review, we found 58 cases; 95% cases accidently ingested leaves of C autumnale instead of A ursinum. Troponin I was reported in 3% cases. The lethality of this and reviewed cases was 35% (26/74). CONCLUSIONS: In unexplained gastroenterocolitis after ingestion of wild plants as a salad or spice in the spring, especially when wild garlic is mentioned, we should always consider C autumnale poisoning. Cardiogenic shock can be predicted by a positive serum troponin I measurement.

Cholinergic syndrome: a case report of acute organophosphate and carbamate poisoning.

Cholinergic syndrome is a common topic at western medical universities yet rarely observed in clinical practice. The treatment involves muscarinic antagonists, acetylcholinesterase reactivation, seizure control, and supportive measures. Here we report a case of a 52-year old Caucasian male who attempted suicide by ingesting a purple crystal powder that turned out to be a mixture of carbofuran and chlormephos. At clinical examination, the patient presented with salivation, perspiration, diarrhoea, bradypnoea, loss of consciousness, and epileptic seizures. Laboratory tests showed low plasma cholinesterase, and we started obidoxime along with supportive intensive care treatment. He was later transferred to the psychiatry department for further diagnostics and treatment.

Yellow sac spider (Cheiracanthium punctorium) bites in Slovenia: case series and review.

In Central Europe, reports of human envenomation by Cheiracanthium punctorium, commonly known as the yellow sac spider, are sporadic, despite the fact that this species is widespread in Europe. However, in recent years, C. punctorium has been repeatedly described globally in medical and toxicological literature. Its venom was found to possess insecticidal, haemolytic, cytotoxic, and membrane-damaging activities. Its bite is often very painful, frequently associated with local and transient cutaneous and neurotoxic effects, but sometimes also with systemic symptoms which require medical help. The main objective of this article is to introduce more details about C. punctorium, the clinical manifestations and circumstances of its bite, the characteristics of its venom and proposed clinical management. The authors provide case reports of patients bitten by C. punctorium during the 10-year observational period. All patients presented in this article showed generally mild clinical manifestations and recovered completely without sequelae. No further treatment in terms of hospital surveillance or specific clinical measures was necessary in any of the reported cases.

Occupational transdermal poisoning with synthetic cannabinoid cumyl-PINACA.

CONTEXT: Synthetic cannabinoids are getting more popular among young people and illicit manufacturers. We report a case series of occupational transdermal poisoning with synthetic cannabinoids. CASE DETAILS: Three customs inspectors got in contact with a sticky substance with their fingertips because they were not wearing protection gloves and the delivered package was damaged. Despite washing their hands with water, signs of synthetic cannabinoids intoxication started occurring half an hour after exposure. On arrival at the Emergency Department six hours later, they were somnolent, lethargic and confused. They showed signs of mydriasis, blurred vision, ataxia, weakness, numbness, tachycardia and one of them had orthostatic hypotension. Two days later, they were feeling much better and reported amnesia and slowed perception of time after exposure. Toxicology analysis by LC-MS/MS revealed synthetic cannabinoid cumyl-PINACA (SGT-24) in their blood samples taken on admission. cumyl-PINACA was also confirmed with NMR method in liquid samples seized at the airport. It was 98% pure substance with the purpose of being diluted and sold further in the drug market by drug dealer. DISCUSSION: This case series highlights the possible transdermal exposure to synthetic cannabinoids oil resulting in prolonged cannabinoid syndrome.

Vipera ammodytes bites treated with antivenom ViperaTAb: a case series with pharmacokinetic evaluation.

CONTEXT: In clinical practice it is difficult to differentiate between V. berus and V. ammodytes venomous bites. In the past this was not a concern, but due to the current shortage in Viperfav™ and European viper venom antiserum availability, V. a. ammodytes venomous bites have recently been treated with ViperaTAb®, which is a pharmaceutical formulation containing a monospecific ovine Fab fragments against the venom of V. berus. OBJECTIVE: To evaluate ViperaTAb® in V. a. ammodytes envenomations. MATERIALS AND METHODS: This is a prospective case series of three consecutive patients envenomed by V. a. ammodytes snakebite treated with ViperaTAb®. V. ammodytes venom, neurotoxic ammodytoxins, and Fab fragment levels were determined in serum samples and a pharmacokinetic analysis of the antivenom Fab fragments was carried out. RESULTS: Three patients bitten by V. a. ammodytes with extensive local swelling, neurological symptoms and recurrent thrombocytopenia were treated with ViperaTAb®. V. ammodytes venom was detected in serum of all three patients. Ammodytoxins were detected in the serum of only the most severely envenomed patient who developed neurological symptoms. In the presented moderate cases, a dose of 8 mL of ViperaTAb® reduced swelling and improved systemic effects, such as thrombocytopenia. However, this dose of ViperaTAb® was not effective in the most severely envenomed patient with the highest serum values of V. ammodytes venom. In this case ViperaTAb® did not stop local swelling and it had no effect on neurological signs. ViperaTAb®'s systemic clearance, distribution and elimination half-lives were 4.3-13.4 mL/h/kg, 1.2-3.2 h and 14.1-55.4 h, respectively. CONCLUSIONS: In patients envenomed by V. a. ammodytes venom, ViperaTAb® reduces moderate swelling and temporarily improves systemic effects, except neurological symptoms. ViperaTAb® application induces a decrement of V. ammodytes venom level in the blood, but did not affect serum concentration of neurotoxic ammodytoxins in the one patient with measurable concentrations.

A Single Dose of Viperfav(TM) May Be Inadequate for Vipera ammodytes Snake Bite: A Case Report and Pharmacokinetic Evaluation.

Viperfav(TM) is a commercial F(ab')2 antivenom prepared against European vipers venom. It is safe and effective for treating envenomation caused by Vipera aspis and Vipera berus. Therapeutic efficacy for treating Vipera ammodytes ammodytes (V. a. ammodytes) envenoming has not been yet described, although protective efficacy has been demonstrated in preclinical studies. We report on a 32-year-old man bitten by V. a. ammodytes who was treated with Viperfav™. Viperfav™ promptly reduced local extension and improved systemic pathological signs, but 24 h after the incident a recurrence of thrombocytopenia occurred despite a favorable pharmacokinetic profile with systemic clearance (1.64 (mL·h(-1))·kg(-1)) and elimination half-life (97 h) among the highest ever reported. The recommended dose of Viperfav™ for V. aspis and V. berus bites may be inadequate for serious V. a. ammodytes envenomations. Following V. a. ammodytes bite, serial blood counts and coagulation profiles should be performed to help guide Viperfav™ treatment, along with supplemental administration as indicated.

Low-dose intravenous lipid emulsion for the treatment of severe quetiapine and citalopram poisoning.

The treatment of quetiapine and/or citalopram poisoning is mainly supportive and involves gastric lavage, activated charcoal, intubation, and mechanical ventilation. Recently, however, there were reports of successful treatment with intravenous lipid emulsion. Here we report a case of a 19-year-old Caucasian girl who ingested approximately 6000 mg of quetiapine, 400 mg of citalopram, and 45 mg of bromazepam in a suicide attempt. The patient developed ventricular tachycardia and epileptic seizures 12 h after admission to the hospital. As the patient's condition deteriorated, we combined standard therapy (intubation, mechanical ventilation, and vasopressors) with low-dose intravenous lipid emulsion (ILE) (a total of 300 mL of 20 % lipid emulsion) and normalised her heart rhythm and stopped the seizures. She was discharged to the psychiatric ward after 48 h and home after a prolonged (2-month) psychiatric rehabilitation. Intravenous lipid emulsion turned out to be effective even in the lower dose range than previously reported for quetiapine poisoning in patients presenting with seizure and ventricular arrhythmia. To our knowledge, there are no case reports describing the use of ILE in treating citalopram poisoning.