Clinical characteristics of acute lacosamide poisoning: Pavia Poison Control Centre experience.

AIMS: Lacosamide is a third-generation antiepileptic drug used as adjunctive therapy for partial seizures. Since its approval in 2008 very few cases of lacosamide overdose have been described in literature. The aim of our study was to evaluate clinical characteristics of acute lacosamide poisoning. METHODS: A retrospective observational study was performed including all cases of acute lacosamide poisoning referred to Pavia Poison Control Centre from January 2012 to December 2021. For each patient age, sex, ingested dose, coingestants, clinical manifestations, treatment and outcome were collected. RESULTS: A total of 31 subjects (median age 39 years, [interquartile range: 26.5-46.5]; females 22/31) were included. The median lacosamide ingested dose was 1500 mg [650-2800]. In 35.5% of cases lacosamide was the single ingested substance, while in 64.5% coingestants were also present. Coingestants varied from a minimum of 1 to a maximum of 3, with the more common being benzodiazepines and valproic acid. Clinical manifestations were present in 87% patients the most common were: vomiting (29%); seizures (29%), coma (25.8%), drowsiness (25.8%), confusion (12.9%), agitation (12.9%), tachycardia (12.9%), tremors (9.7%), bradycardia (9.7%), headache (6.5%) and hypertension (3.2%). The median lacosamide ingested dose was significantly higher in patients that experienced coma compared to patient who did not (2800 vs. 800 mg; P = .0082). Orotracheal intubation was necessary in 32.3% of patients. All patients fully recovered. CONCLUSION: Lacosamide acute overdose may lead to a severe clinical picture. Dentral nervous system symptoms predominated, particularly seizures and coma occurred in a high percentage of cases.

Hydrogen cyanamide exposure: a case series from Pavia Poison Control Centre.

BACKGROUND: Hydrogen cyanamide is a plant growth regulator introduced in Italy as Dormex in 2000, but recalled from the market in 2008. It's currently not authorized in Europe. Inhalation/dermal contact may cause irritation/caustic burns, ingestion of severe organ damage and concomitant alcohol consumption disulfiram-like reaction due to aldehyde-dehydrogenase inhibition by hydrogen cyanamide. AIMS: To study all exposure cases referred to our centre, evaluating temporal and geographic distribution and analysing clinical manifestations, including the ones after alcohol consumption. METHODS: We retrospectively evaluated all hydrogen cyanamide exposures referred to our Poison Control Centre (January 2007-December 2021). For each case, age, sex, exposure route/year, geographical location, intent of exposure, alcohol co-ingestion, emergency department-admission Poison Severity Score, signs/symptoms and treatment were analysed. RESULTS: Thirty subjects were included. Median case/year was 1 [1; 2]: 79% occurred after market withdrawal, 92% in Sicily. All exposures were unintentional and work related; 41% of patients also co-ingested alcohol. Mean poison severity score at emergency department admission was 1.54, more severe when ingestion occurred. The most common signs/symptoms were flushing, secondary to peripheral vasodilation (41%), hyperaemia/erythema (29%), dyspnoea (25%), nausea (20%), vomiting (12%), oedema (12%), II-III degrees burns (12%) and pharyngodynia (12%). All patients were treated symptomatically and fully recovered. CONCLUSIONS: Hydrogen cyanamide exposure can lead to severe clinical manifestations. Despite its withdrawal from the Italian market, hydrogen cyanamide is still used: through PCC's crucial role in monitoring exposure to agricultural products efforts should be made to contrast illegal trade and increase awareness of its potential toxicity in those countries in which it's still legal.

Coronary thrombosis after European adder bite in a patient on dual antiplatelet therapy: A case report.

INTRODUCTION: Until now very few cases of an adverse cardiovascular event have been described following European viper envenomation (Aravanis et al., 1982) (Aravanis et al., 1982) (Aravanis et al., 1982) (Aravanis et al., 1982). In fact, cardiac toxicity following snake bite is rare and primary reported from tropical and subtropical areas with only twenty-one cases of myocardial infarction reported in literature. Herein, we report a case of European viper envenomation associated with coronary artery thrombosis complicated by acute myocardial infarction and cardiac arrest. CASE REPORT: A 62-year-old man, with a history of cardiovascular disease, on dual antiplatelet therapy with ticagrelor and acetylsalicylic acid, was admitted to the Emergency Department, after a bite, on the right hand, from a snake recognized by a herpetologist as a Vipera aspis francisciredi. At ED presentation, 2 hours after the bite, he manifested with vomiting, hypotension (90/60 mmHg) and mild oedema at the bite site. Standard electrocardiogram and troponin were normal at admission. One hour after the admission the patient developed cardiocirculatory arrest (ACC) with return of spontaneous circulation (ROSC) after cardiopolmunary resuscitation. Post ROSC-ECG showed an ST-elevation on anteroseptal and lateral leads and 1-vial of Viper Venom Antitoxin (Biomed®) was i.v. administered. During the next 3 hours three other episodes of ACC occurred, always with restoration of spontaneous circulation. Percutaneous transluminal coronary angiography showed a thrombus on the bifurcation of anterior descending coronary artery and diagonal 1 without an underlined atherosclerotic plaque. Neurologic clinical manifestations also occurred 12 hours after the bite: bilateral ptosis and facial paresthesia and a second vial of the same viper antivenom administered. The patient was discharged after 9 days of hospitalization without sequelae. CONCLUSIONS: Our case show that cardiotoxicity is a rare but possible event after snake envenomation in Europe, even if with mechanisms remains to be studied. Vipera aspis has been known to cause primarily neurotoxic manifestations, but a coagulation factor X activator have also been isolated from its venom. Moreover, a specific serine peptidase that can target both PAR1 and PAR3, that are responsible for alternate pathways of platelet aggregation, have been characterized in the venom of a viper. Coronary thrombosis in our case could thus be secondary to a combination of prothrombotic systemic state and platelets dysfunction, in a patient with predisposing factors. Antivenom specific antidotal therapy role in preventing cardiotoxicity still need to be elucidated, but it remains the mainstay of treatment together with coronary angiography if necessary.

The complex and constantly evolving public health threat of new psychoactive substances in Italy: addressing the main functions of a national observatory of drugs.

At the end of the 90s in Europe, the new psychoactive substances (NPS) phenomenon was limited to a small number of molecules created to mimic the actions and psychoactive effects of licensed medicines and existing drugs that are controlled by the United Nations drug conventions and therefore traded as their "legal" replacements. NPS were mostly circulating in rave parties and electronic music festivals. The globalization, the evolution of e-commerce and the growing popularity of NPS, facilitated the development of a wide illegal market in constant expansion. The dynamic nature of this phenomenon has led to an evolution in the prevention and monitoring of NPS trafficking within the European Union. The European legislative system has been amended with the aim of creating a faster and more effective regulatory system to tackle NPS diffusion and ban their sale and circulation. At the end of 2008, in compliance with the European Council Decision 2005/387/JHA, the Anti-Drug Policies Department of the Presidency of the Council of Ministers activated the National Early Warning System to promote a rapid exchange of information on NPS between Italy and the EU.

Prevalence of Stimulant, Hallucinogen, and Dissociative Substances Detected in Biological Samples of NPS-Intoxicated Patients in Italy.

A number of new psychoactive substances (NPS) have been released in the last decade, and the list of NPS continues to grow. This paper reports a retrospective evaluation of the toxicological analyses in 1,445 suspected intoxication cases by psychostimulant, hallucinogen, and dissociative NPS occurring in hospitals across Italy from 2011 to 2019. The objectives of the study were to contribute to the monitoring of the NPS diffusion based on analytically confirmed intoxications, and to evaluate the importance of the clinical toxicological laboratory in the diagnosis of NPS intoxication. For at least one NPS of the considered classes, 246 patients (17.0%) tested positive. Forty-four different NPS were detected and a consistent turnover was observed during the nine-year period, especially regarding cathinones. Among the positive cases, 47.2% tested positive for dissociative NPS, with particular regard to ketamine. Hallucinogens (30.9%) was the second most frequent NPS involved. Stimulants were found in 20% of the positive cases with a considerable presence of cathinones. Findings confirm the dynamism of the NPS phenomenon, underline the importance of awareness of this new public health threat among health care professionals, and highlight the need for analytical confirmation for the identification of the drugs in forensic contexts.

Poisoning related to therapeutic error in prolonged low-dose methotrexate treatment.

AIMS: To study the predictive factors for the development of clinical manifestations in poisoning due to the erroneous taking of low-dose methotrexate (MTX). METHODS: A retrospective observational study was performed. Only cases of erroneous administration in non-oncologic outpatients were included (July 2008-March 2020). RESULTS: Forty-one cases were included. All patients were taking MTX for the first time. In 36 cases, patients took MTX daily instead of weekly. In the other five patients, MTX was sold instead of methylergometrine. Clinical manifestations were absent in 12/41 patients (29.3%). All 29 (70.7%) symptomatic patients recognized the medication error when they developed clinical manifestations: dermatological, haematological and gastrointestinal symptoms. Statistical results showed that symptomatic patients were older, received a higher amount of total dose and were treated for longer. Moreover, the probability of being symptomatic increases as a function of age and of total dose. Asymptomatic patients were treated with folinic acid (30 mg/m2 /day) for 5 days. Symptomatic patients were treated with folinic acid together with treatments for the specific clinical manifestations. No patients were treated with glucarpidase. All patients fully recovered. CONCLUSIONS: When MTX is prescribed for the first time, it is important to clearly communicate with patients to avoid therapeutic errors. In our experience, age, total dose taken and number of days of assumption are predictive for the presence/absence of clinical manifestations. These parameters must be evaluated together to identify patients needing maximum starting treatment with folinic acid and closer monitoring.

Foodborne Botulism: Clinical Diagnosis and Medical Treatment.

Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All different forms are characterized by the same symptoms, caused by toxin-induced neuromuscular paralysis. The diagnosis of botulism is essentially clinical, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. Foodborne botulism intoxication is often underdiagnosed; the initial symptoms can be confused with more common clinical conditions (i.e., stroke, myasthenia gravis, Guillain-Barré syndrome-Miller-Fisher variant, Eaton-Lambert syndrome, tick paralysis and shellfish or tetrodotoxin poisoning). The treatment includes procedures for decontamination, antidote administration and, when required, support of respiratory function; few differences are related to the different way of exposure.

Exposure to Nail and False Eyelash Glue: A Case Series Study.

The use of artificial nail tips in professional manicure services and the application of false eyelashes are a growing trend among young women. Often, this "beauty routine" is performed at home without the supervision of an expert beautician, raising health problems due to either the spillage of these products or to accidental exposure to children. The aim of this study is to review the Pavia Poison Control Centre clinical records to identify the frequency, the most common route of exposure, and the possible risks associated to these events to support the decision-making process in emergency departments. The Pavia Poison Control Centre database was retrospectively searched for records reporting nail or false eyelash glue exposure from January 2007 to April 2020, and 42 patients were identified. Among the patients, 76% presented symptoms from mild to severe, while 24% were asymptomatic. The most common route of exposure was dermal, through cutaneous contact, as determined for 19 patients involved. Among these, seven patients presented with second-degree chemical burns, cutaneous erythema, and ocular symptoms. The most dangerous glue component was cyanoacrylate, leading to symptoms in 16 out of 22 patients, while three cases remained asymptomatic. Even if this exposure is relatively rare, nail and false eyelash glue can be seriously harmful, especially when exposure occurs via dermal or ocular routes. In the case of emergency, it is important to treat the patient as fast as possible to limit the damage caused by a burn. Moreover, even though these products are often perceived as harmless, safety precautions should be taken to prevent children from accidental contact.

Latrodectism in Italy: First report of successful treatment of L. tredecimguttatus envenomation using L. mactans antivenom from North America.

INTRODUCTION: Latrodectism is a rare, but potentially severe, clinical syndrome caused by spider of the genus Latrodectus. L. tredecimguttatus is widespread in Italy and its bite cause the injection of α-latrotoxin that cause depletion of acetylcholine at motor nerve endings and release of catecholamines at adrenergic nerve endings. We describe the first clinical case of L. tredecimguttatus poisoning successfully treated with L. mactans antivenom from North America. CASE REPORT: A healthy 60-year-old patient was admitted to the emergency department after unknown insect sting or arachnid/snake bite. In the early morning, the patient was working in the countryside when he felt a sting-like pain in the medial area of the right lower leg, associated with an intense burning sensation. An hour later he developed agitation, hoarseness, sweating, abdominal distress and intense pain in his right leg. In the emergency room vital signs showed a hypertensive crisis, tachycardia and peripheral oxygen desaturation. ECG was normal and ABE showed mixed acid-base disorder. Blood tests showed leukocytosis with neutrophilia, high levels of myoglobin, with normal coagulation and normal plasmatic cholinesterase. Neck, thorax and abdomen CT scan, with and without contrast medium, was negative. Four hours after admission hypertension worsened with board like rigid abdomen and onset of fasciculations, tremors, miosis and intense regional sweating. The definitive diagnosis of poisoning by L tredecimguttatus was based on the clinical picture. Within short time the antidote was provided by the Poison Centre and administered. A marked improvement of the symptomatology was noted after 30 minutes, and 1 hour later all symptoms were under control. The patient was discharged after 2 days. CONCLUSIONS: The clinical presentation of a patient suffering from latrodectism places the clinician in front of a challenging differential diagnosis. Following the suspicion, the first-line doctor is invited to discuss the case with a toxicologist, in order to confirm or exclude the diagnosis and implement all therapeutic measures. In our clinical case, the absence of organic lesions, laboratory tests not suggestive for other causes, and the presence of typical clinical feature suggested the diagnosis of L tredecimguttatus poisoning. This hypothesis was then supported by the close temporal relation between antivenom administration and symptoms improvement. With this case, we report the first use of L mactans antivenom from North America to treat L.tredecimguttatus poisoning and we confirm its effectiveness in counteracting latrodectism caused by this spider.