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This study aimed to assess the role of the laboratory of toxicology as a support for a correct diagnosis of intoxication through the application of a reliable analytical approach, critically designed to meet pediatric needs.Data collected from 360 cases of suspected intoxications in pediatric patients (aged 1 day to 17 years) during the period 2018 to 2019 are presented. Toxicological analyses were performed through different techniques (immunoassay and chromatography) with parameters (limit of detection and cut-off) adjusted according to pediatric needs to produce reliable toxicological data for a wide number of prescription drugs, drugs of abuse, and poisons.We present results about (1) agents involved in suspected poisonings and the methods adopted for a definite analytical diagnosis, (2) the assessment of the concordance of results for analyses proceeded by different techniques, and (3) the percentage of agreement between analytical result and clinical suspicion.An analytical approach critically designed to minimize misinterpretation of laboratory data and able to provide reliable results for a wide number of substances in a time compatible with the urgency represents a useful support for a correct diagnosis of intoxication in pediatrics.

Mushroom poisoning is an important cause of intoxication worldwide. The toxic mechanism remains frequently unknown and the diffusion of non-endemic species may cause the emergence of new syndromes. An example is the widespread of Chlorophyllum molybdites in Sicily.Pavia Poison Centre was recently involved in the management of 10 intoxications caused by the ingestion of Chlorophyllum molybdites, which was not considered part of the Italian mycological species. The clinical syndrome was characterized by severe gastrointestinal symptoms. In paediatric or vulnerable patients, it may bring to hypovolemic shock that necessitate intensive support. The possibly confusion with amatoxins-containing mushrooms may complicate the management.Chlorophyllum molybdites is widespread on the oriental coast of Sicily and it could be confused with "parasol mushrooms". Cooperation between emergency physicians, clinical toxicologist and mycologist, supported by improving of laboratory tests, is essential for the appropriate clinical management. Climate changes and migration flows can interfere with the diffusion of new species and the development of novel syndromes.

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.

In clinical toxicology, gastric endoscopic decontamination is rarely used, and only a few cases of pharmacobezoar removal after intentional ingestion of slow-release drugs have been described. Our case describes the use of gastric endoscopic decontamination to remove potential pharmacobezoar in an adolescent after ingestion of a lethal dose of isoniazid and rifampin, even long after gastric lavage. This technique allowed the removal of pharmacobezoars still present in the stomach while preventing further deterioration of the patient.

Background In response to the COVID-19 health emergency, mass media widely spread guidelines to stop the virus transmission, leading to an excessive and unaware use of detergents and disinfectants. In Italy and in other countries this tendency caused a significant increase of exposures to these products in 2020. Evaluating data collected by the Italian Pavia Poison Centre (PPC), this study intends to examine the relationship between the COVID-19 lockdown and the variations of exposures to specific product categories possibly associated to the containment measures implemented. Simultaneously, this work shows the effectiveness of the European Product Categorisation System (EuPCS) in surveillance activities of dangerous chemicals. Methods Exposure cases managed by the PPC during March–May 2020 (lockdown) and during the same months of 2017–2018-2019 were compared. Differences in categorical variables were tested with the Chi-square test. The level of significance was set at Alpha = .05. The study included all EuPCS groups but specifically focused on cleaners, detergents, biocides and cosmetics. Results During the lockdown, calls from private citizens showed a highly significant increase (+ 11.5%, p p = .011). Among Cleaners, exposures to Bleaches slightly increased while Drain cleaning products went through a significant reduction (− 13.9%, p = .035). A highly significant increase of exposures to Disinfectants was observed (+ 7.7%, p = .007), particularly to those for surfaces (+ 6.8%, p = .039). Regarding Cosmetics, both handwashing soaps and gel products significantly increased (respectively: + 25.0, p = .016 and + 9.7%, p = .028). Among children 1–5 years, the statistical significance is reached with exposures to Dishwashing detergents (+ 13.1%, p = .032), handwashing soaps (+ 28.6%, p = .014) and handwashing gel products (+ 16.8%, p = .010). Contrarily, Liquid Laundry Detergent Capsules decreased in a highly significant manner (− 25%; p = .001). The general severity of exposures showed a highly significant decrease (Moderate: − 10.1%, p = .0002). Conclusions This study investigated the relationship between the COVID-19 lockdown and the variations of exposures to some product categories related to the containment measures. The results obtained support any action to be taken by Competent Authorities to implement measures for a safer use of cleaners/disinfectants. This paper shows the benefit in applying the EuPCS to categorize products according to their intended use, though an extension of this system to products not covered by CLP Regulation may be a further advantage.

Introduction: Chemical burns are a risk in domestic and occupational accidents due to the common use of caustic agents. Long-term sequelae are normally due to the amount of skin and underlying tissues damaged. We describe a case of work-related chemical burns with unusual evolution in guttate psoriasis. Case Report: A 36 years-old man was admitted to the Emergency Department (ED) three-hours after a work accident. During the cleaning of an industrial hydraulic system, a jet of hydrochloric acid 20% injured his face and upper limbs. At ED admission, he presented first and second-degree skin burns on the frontal region, on the scalp, on the right forearm, and earlobe. Plastic surgery management consisted in wound topical dressing with silver sulfadiazine and paraffin gauze twice a week for one month. Forty-eight hours after the latter topical treatment (45-days after the work accident), in the same anatomical regions of the previous burn scars, he developed a skin reaction with itchy erythema. The application of topical products was suspended without improvement, excluding an allergic reaction. Within few days, a generalized guttate psoriasis was evident on the whole body. Discussion: Despite many prevention actions, work-related burns are a relatively common cause of hospitalization and may involve up to 80% of patients admitted to a burn unit. Guttate psoriasis has not been described as a sequelae of chemical burns. In our case, the others most frequent factors causing guttate psoriasis have been ruled out. Considering the temporal link between the development of guttate psoriasis and the work accident, hydrochloric acid skin burns might have promoted the systemic inflammatory mediators’ mechanism involved in the development of guttate psoriasis lesion’s after the dermal injury.

Considering the consequences on human health, in general population and workplace, associated with the use of new psychoactive substances and their continuous placing on the market, novel in vitro models for neurotoxicology research, applying human-derived CNS cells, may provide a means to understand the mechanistic basis of molecular and cellular alterations in brain. Cytotoxic effects of MAM-2201, a potent-naphthoyl indole derivative-synthetic cannabinoid, have been evaluated applying a panel of human cell-based models of neurons and astrocytes, testing different concentrations (1–30 µM) and exposure times (3–24-48 h). MAM-2201 induced toxicity in primary neuron-like cells (hNLCs), obtained from transdifferentiation of mesenchymal stem cells derived from human umbilical cord. Effects occurred in a concentration- and time-dependent manner. The lowest concentration affecting cell viability, metabolic function, apoptosis, morphology, and neuronal markers (MAP-2, NSE) was 5 μM, and even 1 μM induced apoptosis. Effects appeared early (3 h) and persisted after 24 and 48 h. Similar behavior was evidenced for human D384-astrocytes treated with MAM-2201. Differently, human SH-SY5Y-neurons, both differentiated and undifferentiated, were not sensitive to MAM-2201. On D384, the different altered endpoints were reversed, attenuated, or not antagonized by AM251 indicating that CB1 receptors may partially mediate MAM-2201-induced cytotoxicity. While in hNLCs, all toxic effects caused by MAM-2201 were apparently unrelated to CB-receptors since they were not evidenced by immunofluorescence. The present in vitro findings demonstrate the cytotoxicity of MAM-2201 on human primary neurons (hNLCs) and astrocytes cell line (D384), and support the use of these cellular models as species-specific in vitro tools suitable to clarify the neurotoxicity mechanisms of synthetic cannabinoids.

Dear Editor,We appreciate the feedback and comments provided by Giampreti and Bacis [1]. The key points in our reported case were the decision-making process, and the eventual management of the pot...

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.

Infant botulism is a rare and underdiagnosed disease caused by BoNT-producing clostridia that can temporarily colonize the intestinal lumen of infants less than one year of age. The diagnosis may be challenging because of its rareness, especially in patients showing atypical presentations or concomitant coinfections. In this paper, we report the first infant botulism case associated with Cytomegalovirus coinfection and transient hypogammaglobulinemia and discuss the meaning of these associations in terms of risk factors. Intending to help physicians perform the diagnosis, we also propose a practical clinical and diagnostic criteria checklist based on the revision of the literature.

Viper bites are rare but represent a medical emergency that should not be underestimated both in the paediatric and adult population. The clinical presentation can vary from mild symptoms limited to the venom inoculation site to serious cases with extensive tissue involvement and with systemic neurological, haematologic, renal and cardiovascular symptoms. Immediate hospitalization with clinical monitoring is required to promptly undertake the therapy with antivenom serum, when needed, in order to avoid complications related to the venom’s toxicity. In the literature there are no recent and standardised guidelines on viper bite management and treatment. The paper presents a case-series of four children brought to the Emergency Department for viper bite. The peculiarity of the reported cases is that they were all observed in the first 20 days of May 2020, immediately after the end of the lockdown for Covid-19 pandemic. This could be explained by the effect of prolonged lockdown on animal and viper re-expansion in areas with usually larger human presence. The aim of this article is to present the latest literature updates and provide clear and simple indications for the diagnosis, monitoring and therapy of paediatric viper bite to improve its management and prognosis.

To the Editor Management of caustic ingestion is challenging. To date, the optimal investigations to assess the gastroesophageal injury and decide the optimal strategy of management still fail to r...

To the editor,Herein we describe a case of a 46-year-old pregnant woman (7 weeks + 4 days) with a bilateral metal-on-metal (MoM) hip arthroplasty (2009 right hip, 2010 left hip), with high blood co...

A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology.

Medically relevant cases of snakebite in Europe are predominately caused by European vipers of the genus Vipera. Systemic envenoming by European vipers can cause severe pathology in humans and different clinical manifestations are associated with different members of this genus. The most representative vipers in Europe are V. aspis and V. berus and neurological symptoms have been reported in humans envenomed by the former but not by the latter species. In this study we determined the toxicological profile of V. aspis and V. berus venoms in vivo in mice and we tested the effectiveness of two antivenoms, commonly used as antidotes, in counteracting the specific activities of the two venoms. We found that V. aspis, but not V. berus, is neurotoxic and that this effect is due to the degeneration of peripheral nerve terminals at the NMJ and is not neutralized by the two tested antisera. Differently, V. berus causes a haemorrhagic effect, which is efficiently contrasted by the same antivenoms. These results indicate that the effectiveness of different antisera is strongly influenced by the variable composition of the venoms and reinforce the arguments supporting the use polyvalent antivenoms.

Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders.We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists. At age 23, he developed social withdrawal after being assaulted by a stranger, but did not consult psychiatrists until age 26; during this period, he was using internet-purchased methoxetamine and ketamine, and was persecutory, irritable, suspicious, and insomniac and discontinued all received medical prescriptions. He added dextromethorphan to his list of used substances. At age 31, while using phencyclidine, and, for the first time, methoxphenidine, he developed a religious delusion, involving God calling him to reach Him, and the near-death experiences ensured by NMDA antagonists backed his purpose. He received Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnosis of multisubstance-induced psychotic disorder and was hospitalized 8 times, 6 of which after visiting the emergency room due to the development of extreme anguish, verbal and physical aggression, and paranoia. He reportedly used methoxphenidine, methoxyphencyclidine, ethylnorketamine, norketamine, and deschlorketamine, to achieve near-death experiences, and eventually to reach God in heavens.This case points to the need for better control of drugs sold on the internet. It also illustrates that people using NMDA antagonists may present clinical pictures indistinguishable from those of major psychoses and are likely to be misdiagnosed.

A method for the quantitation of α-fluoro-β-alanine (AFBA), the main metabolite of capecitabine (Cape) and 5-fluoruracil (5-FU), is described. Among antineoplastic drugs (ADs), 5-FU and Cape (the new oral prodrug) are the most commonly applied drugs in cancer therapy. The main objective of this study was to develop a reliable method that would be easy to run on a reversed-phase UHPLC system coupled to tandem mass spectrometry. AFBA was derivatized with Sanger's reagent to ensure complete yield of a stable 2,4 dinitrophenil-α-fluoro-β-alanine derivative. This method was based on the use of a mixed-mode anion exchange solid phase extraction enabling urinary extracts to be clear of endogenous interferences affecting quantitative results. The assay was validated in human urine according to FDA criteria with the use of a labeled internal standard (β-alanine-d4) to minimize experimental error. Good accuracy and precision were demonstrated by determining spiked urine QC samples in four consecutive days. The recovery of AFBA was between 70.0 and 82.6%, with a matrix effect that was 12.8%–18.5%. The lower limit of quantitation (LOQ) was 0.5 ng/mL with a coefficient of variation of 5.3%. This assay was successfully applied to determine the levels of this metabolite in a large number of urine samples taken from personnel who were occupationally exposed to ADs.

Ciguatera fish poisoning (CFP) is the most prevalent non-bacterial food-borne form of poisoning in French Polynesia, which results from the consumption of coral reef fish naturally contaminated with ciguatoxins produced by dinoflagellates in the genus Gambierdiscus. Since the early 2000s, this French territory has also witnessed the emergence of atypical forms of ciguatera, known as ciguatera shellfish poisoning (CSP), associated with the consumption of marine invertebrates. In June 2014, nine tourists simultaneously developed a major and persistent poisoning syndrome following the consumption of the gastropod Tectus niloticus collected in Anaho, a secluded bay of Nuku Hiva Island (Marquesas Archipelago, French Polynesia). The unusual nature and severity of this event prompted a multidisciplinary investigation in order to characterize the etiology and document the short/long-term health consequences of this mass-poisoning event. This paper presents the results of clinical investigations based on hospital medical records, medical follow-up conducted six and 20 months post-poisoning, including a case description. This study is the first to describe the medical signature of T. niloticus poisoning in French Polynesia and contributed to alerting local authorities about the potential health hazards associated with the consumption of this gastropod, which is highly prized by local communities in Pacific island countries and territories.

Although in the last few decades, titanium dioxide nanoparticles (TiO2NPs) have attracted extensive interest due to their use in wide range of applications, their influences on human health are still quite uncertain and less known. Evidence exists indicating TiO2NPs ability to enter the brain, thus representing a realistic risk factor for both chronic and accidental exposure with the consequent needs for more detailed investigation on CNS. A rapid and effective in vitro test strategy has been applied to determine the effects of TiO2NPs anatase isoform, on human glial (D384) and neuronal (SH-SY5Y) cell lines. Toxicity was assessed at different levels: mitochondrial function (by MTT), membrane integrity and cell morphology (by calcein AM/PI staining) after acute exposure (4–24–48 h) at doses from 1.5 to 250 μg/ml as well as growth and cell proliferation (by clonogenic test) after prolonged exposure (7–10 days) at sub-toxic concentrations (from 0.05 to 31 μg/ml). The cytotoxic effects of TiO2NPs were compared with those caused by TiO2 bulk counterpart treatment. Acute TiO2NP exposure produced (i) dose- and time-dependent alterations of the mitochondrial function on D384 and SH-SY5Y cells starting at 31 and 15 μg/ml doses, respectively, after 24 h exposure. SH-SY5Y were slightly more sensitive than D384 cells; and (ii) cell membrane damage occurring at 125 μg/ml after 24 h exposure in both cerebral cells. Comparatively, the effects of TiO2 bulk were less pronounced than those induced by nanoparticles in both cerebral cell lines. Prolonged exposure indicated that the proliferative capacity (colony size) was compromised at the extremely low TiO2NP doses namely 1.5 μg/ml and 0.1 μg/ml for D384 and SH-SY5Y, respectively; cell sensitivity was still higher for SH-SY5Y compared to D384. Colony number decrease (15%) was also evidenced at ≥0.2 μg/ml TiO2NP dose. Whereas, TiO2 bulk treatment affected cell morphology only. TiO2 internalization in SH-SY5Y and D384 cells was appreciated using light microscopy. These findings indicated, that (i) human cerebral SH-SY5Y and D384 cell lines exposed to TiO2NPs were affected not only after acute but even after prolonged exposure at particularly low doses (≥ 0.1 μg/ml), (ii) these in vitro critical doses were comparable to literature brain Ti levels detected in lab animal intranasally administered with TiO2NP and associated to neurotoxic effects. In summary, the applied cell-based screening platform seems to provide effective means to initial evaluation of TiO2NP toxicity on CNS.

A patient suffered from an envenomation that, at his hospitalization, was judged severe: Grade 3 out of 3, as defined in clinical studies for CroFab™ antidote [Crotalidae Polyvalent Immune Fab (Ovine)]. In addition to the usual antivenom treatment we applied adjunctive hyperbaric oxygen (HBO₂) therapy. Our aim was to facilitate better control of the lesions, already presenting as problematic wounds and at high risk of necrotizing soft tissue infection with compartment aspects. The regimen consisted of six treatments, one daily at 2.4 atmospheres absolute at 25 minutes x3 (75 minutes) at FiO₂=1, with two five-minute air breaks interposed. The therapy was well tolerated in spite of the patient's declared trait of claustrophobia. Our findings at a long-term follow up suggest that HBO₂ therapy may be reasonably and effectively administered at least in the post-acute phase of such occurrences.

Ingestion of elemental mercury (Hg0) is considered non-toxic. After massive ingestion, local intestinal complications may develop: retention within appendix is quite frequent but treatment is debated. We describe a case of intentional ingestion of Hg0 requiring multi-step decontamination and prophylactic appendectomy. Case detail: A 19-year-old woman was admitted to ED for abdominal pain. History revealed ingestion of large amount of Hg0 as suicide attempt. To prevent absorption, facilitate elimination, and avoid complications a conservative approach was started. Due to inefficacy of initial maneuvers colonoscopy with irrigation/aspiration was performed, repeated whole bowel irrigation was continued and second colonoscopy was performed to clean residual metal. Abdominal plain films confirmed the presence of retained mercury within the appendix in asymptomatic patient. To reduce risk of appendicitis, potential perforation, and possibly systemic toxicity, a prophylactic laparoscopic appendectomy was performed at day 5 with removal of all retained mercury without peritoneal spillage. Highest mercury concentration was 22.7 mcg/L in serum (1-4.5 mcg/L) and 5.1 mcg/L in urine (0.1-5 mcg/L).After ingestion, metal retention in appendix is quite frequent. Evidence about optimal treatment are different and based on case reports. A multi-step approach with multidisciplinary evaluation tailored to the patient is suggested.

Botulism is a rare but severe neuroparalytic disease caused by botulinum toxins. Because of its high potential impact on public health, botulism is a closely monitored communicable disease in Europe. In Italy, which has one of the highest incidence rates in Europe (0.03 cases per 100,000 population), botulism is monitored through a case-based passive surveillance system: the front-line physician who diagnoses a suspected case must notify the Local Health Units immediately, and the Ministry of Health's office within 12 hours. From 1986 to 2015, 466 confirmed cases of botulism were recorded in Italy (of 1,257 suspected cases). Of these, 421 were food-borne (the most frequently seen form of botulism due to the consumption of improperly home-canned foods), 36 were infant botulism, which accounts for ca 50% of all these types of cases registered in Europe, six were wound-related and three were due to adult intestinal colonisation. This scenario suggests that stronger efforts should be made towards raising public awareness of the risk of food-borne botulism, especially with respect to home-preserved foods, as well as improving the training of front-line medical personnel, to ensure that a quick and accurate diagnosis of botulism can be made.

Background: European viper bite is relatively uncommon but can cause serious envenoming, particularly swelling and hemorrhage spreading from limb to trunk that can cause long term disability. Systemic features are relatively mild compared to many other venomous species. Moderate-to-severe envenoming requires antivenom, which is given many hundreds of times each year across the continent. Several Vipera spp antivenoms are produced in Europe, but there is little comparative information available for the antivenoms and none is licensed with the European Medicines Agency. We aimed to collect descriptive data on European viper antivenoms and assess their relative effectiveness. Methods: A systematic review of articles relating to antivenom in Europe was performed using the Medline medical database. The following keywords “Europ*” or the individual names of each European country and “antiven*” or “immun*” or “envenom*” and “snake” or “viper*” or “adder” were used. Articles published between 1 January 1996 and 11 March 2016 pertaining to clinical outcome, including case reports, were selected. Referenced articles in the indexed articles were explored for suitability and included if they met any of the criteria: specific antivenom used, route of antivenom administration, adverse reactions to antivenom therapy and length of hospital admission. All accepted abstracts from EAPCCT conferences since 2000 were searched and abstracts relating to Vipera spp envenoming were assessed for suitability. We extracted data on study type, safety and effectiveness. We sought information on antivenoms from manufacturers and individual patient data from authors of publications. Since individual patient data were only rarely available, we compared median length of stay between case series reporting each antivenom. We identified 40 papers and six published abstracts, and one unpublished paper that reported clinical cases and case series of envenomed patients treated with antivenom. No publication reported randomized controlled trials comparing any European Vipera antivenom with either placebo or another antivenom. 25 reports were of retrospective hospital- (n = 13) or poison center-based (n = 12) case series including five or more patients; a further 12 reports were either case reports or case series with less than five patients and one paper was a limited literature review. An additional nine papers reported prospective data; seven collected data remotely through poison service telephone communication with the attending physicians. Antivenoms available in Europe: Eight antivenoms are available for European Vipera spp envenoming; a material safety data sheet providing information on manufacture was available for seven. Six are raised against V. berus or V. ammodytes venom; the seventh is raised against a mixture of V. ammodytes, V. aspis and V. berus venom and the eighth is raised against V. ammodytes, Macrovipera lebetina and Montivipera xanthina venom. Six manufacturers recommended intramuscular administration while two recommended intravenous administration. No randomized control trials comparing the effectiveness of antivenoms were identified. Pre-clinical data: We found two papers presenting comparative preclinical data. Clinical data: Clinical studies were predominantly retrospective and contained clinical data on antivenom used in 2602 patients; where the antivenom was identified (n = 2174), 2061 (94.8%) received Zagreb, ViperFAV or ViperaTAb antivenoms. There were few published data on the other antivenoms. Repeated use of antivenom: Repeat doses were reported in 230/1491 of cases (15.4%) where this information was recorded. Outcome and length of hospital stay: Intravenous administration of antivenom was associated with shorter length of hospital stay (median length of hospital stay in studies of intravenous ViperFAV or ViperaTAb ranged from 1 to 4.8 days versus 2 to 18 days for intramuscular Bulbio or Zagreb antivenoms). Antivenom versus no antivenom: Some small studies demonstrated no difference in the length of hospital stay in patients with equivalent envenomation grading who either did or did not receive antivenom. Adverse events: Adverse reactions were reported in 37 of 2408 cases (1.5%) including seven cases of anaphylaxis. Conclusions: There are very limited pre-clinical comparative data and no randomised controlled trials assessing effectiveness of the antivenoms against different Vipera species. Most descriptive data suggest the efficacy of Zagreb, ViperFAV and ViperaTAb antivenoms by the intravenous route but not intramuscular route, although this is level D evidence. Reported adverse reactions were rare, suggesting that the modern intravenous antivenoms are of good quality. Better and more systematic data, including perhaps randomized controlled trials comparing different antivenoms, are required for the many hundreds of antivenom administrations that occur annually across Europe.