Current Awareness in Clinical Toxicology Editors: Damian Ballam MSc and Allister Vale MD April 2017 CONTENTS General Toxicology 10 Metals 38 Management 21 Pesticides 39 Drugs 23 Chemical Warfare 41 Chemical Incidents & 33 Plants 42 Pollution Chemicals 33 Animals 42 CURRENT AWARENESS PAPERS OF THE MONTH Antivenom for European Vipera species envenoming Lamb T, de Haro L, Lonati D, Brvar M, Eddleston M. Clin Toxicol 2017; online early: doi: 10.1080/15563650.2017.1300261: 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 Current Awareness in Clinical Toxicology is produced monthly for the American Academy of Clinical Toxicology by the Birmingham Unit of the UK National Poisons Information Service, with contributions from the Cardiff, Edinburgh, and Newcastle Units. The NPIS is commissioned by Public Health England 2 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 3 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. Full text available from: http://dx.doi.org/10.1080/15563650.2017.1300261 Toxicity from fluoropolymer-containing grout, tile and stone floor sealants reported to the UK National Poisons Information Service 2009–2015 Henke D, Campbell A, Bradberry SM, Sandilands EA, Thomas SHL, Thompson JP, Vale JA. Clin Toxicol 2017; online early: doi: 10.1080/ 15563650.2017.1296154: Context Grout, tile and floor stone sealants contain a solvent, a water-repelling agent and in the case of aerosols a propellant. The water-repelling agent used is typically a fluoropolymer resin, a silicon-based resin, or a combination of both. Objective To report the clinical course in patients exposed to fluoropolymer-containing sealants referred to the United Kingdom National Poisons Information Service. Methods A retrospective analysis was performed of telephone enquiries received between 2009 and 2015. Results 101 enquiries involving 96 exposures were received. The majority of the exposures (n = 88) occurred when the sealant was delivered from an aerosol. Twelve patients were exposed occupationally and the remainder were exposed while using the product at home. Eighty- nine exposures were as a result of inhalation alone, two followed ingestion, three skin contact and one eye contact; one involved inhalation and eye contact. All 90 patients exposed by inhalation developed clinical features: 31 had a World Health Organisation/ International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score of 1 (minor toxicity), 51 patients had features of moderate toxicity (PSS 2) and eight were graded PSS 3 (severe poisoning). The most common features were dyspnea (n = 52; 57.8%; 95% CI = 47.0– 68.5), chest pain/tightness (n = 34; 37.8%; 95% CI = 27.2–48.4), coughing (n = 27; 30.0%; 95% CI = 20.0–40.0) and sinus tachycardia (n = 11; 12.2%; 95% CI = 4.1–18.2); hypoxemia was present in 20 (22.2%; 95% CI = 13.1–31.4). At the time of the enquiry a chest X-ray had been performed on 15 patients: in eight patients (all of whom were PSS 3) the X-ray was reported as being abnormal and showed bilateral shadowing. Conclusions This study demonstrates that if fluoropolymer-containing sealants are inhaled then clinical features may occur and in a small proportion (9%) these features may be severe. Full text available from: http://dx.doi.org/10.1080/15563650.2017.1296154 4 Underestimated impact of novel psychoactive substances: laboratory confirmation of recreational drug toxicity in Oslo, Norway Vallersnes OM, Persett PS, Øiestad EL, Karinen R, Heyerdahl F, Hovda KE. Clin Toxicol 2017; online early: doi: 10.1080/15563650.2017.1312002: Context Recreational drug toxicity is frequent. Availability of new psychoactive substances is steadily increasing. However, data with verified analyses from clinical settings are limited. To evaluate the impact of novel psychoactive substances (NPS) on recreational drug toxicity in Oslo, Norway, we analysed samples from a selection of patients. Methods All the patients presenting with recreational drug toxicity at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) and at the Oslo University Hospital (OUH) were registered from April through September 2014. Oral fluid samples were collected at the OAEOC. Blood samples were collected at the OUH. The samples were screened using ultra- high performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS). Results Nine hundred and sixty-four cases were included, 841 (87.2%) at the OAEOC and 123 (12.8%) at the OUH. A total of 55 oral fluid samples (OAEOC) and 103 blood samples (OUH) could be analysed. NPS were not clinically suspected in any of the screened cases. At the outpatient clinic, the most commonly found substances were clonazepam in 42/55 (76.4%) cases, amfetamines in 40/55