Paediatric opioid poisoning in the UK: a retrospective analysis of clinical enquiries to the National Poisons Information Service.

OBJECTIVE: To evaluate a decade of reported paediatric opioid poisoning cases in the UK. METHODS: The National Poisons Information Service (NPIS) telephone enquiries database (UK Poisons Information Database) was searched for calls regarding opioid poisoning in children under 18 years from 2012 to 2021. The NPIS online clinical guidance database TOXBASE was searched for accesses relating to opioids for both adults and children. The Office of National Statistics provided paediatric data for hospital admissions and deaths in those aged under 20 years old due to opioids. RESULTS: The NPIS received 426 774 telephone enquiries from 2012 to 2021 from across the UK, 3600 in relation to opioid exposures regarding children under 18 years. Annual telephone enquiries regarding paediatric opiate poisoning reduced year on year, from around 450 to 300 calls/year. A rise in all age TOXBASE annual accesses relating to opioids from 71 642 in 2012 to 87 498 in 2021 was noted, a total of 838 455 during the study period. Hospital admissions from opioid poisoning remained consistent, with around 1500 admissions/year. Deaths were uncommon, but averaged 18 deaths annually. Co-codamol was the most reported substance to NPIS, with 1193 calls (36.5%), followed by codeine with 935 (26.1%). CONCLUSIONS: Opioid poisoning in children is not uncommon. There is a general downward trend in telephone enquiries to NPIS, but many childhood exposures may have been dealt with through consultations via TOXBASE, where accesses relating to opioids have increased. Unfortunately, children still die from opioid exposure each year in the UK and this figure has changed little during 2012-2021.

Investigation and monitoring of heavy metal poisoning.

Historically, heavy metal measurement and interpretation has been a highly specialised area performed only in a handful of centres within the UK. However, recent years have seen a move to more local testing due to the repatriation of referred work into pathology networks and the increased availability of inductively coupled plasma mass spectrometry technology. While management of significant poisoning is still overseen by tertiary care poisoning specialists, management of milder cases may be undertaken locally.Non-specialist clinical scientists and clinicians need to know when heavy metal testing is appropriate, which samples are required (and any specific requirements around collection) and how to interpret and act on the results.This Best Practice article provides guidance on the investigation and monitoring of the toxic elements most frequently encountered in general medical practice; lead, mercury and arsenic. It is intended as a reference guide for the non-specialist and as a comprehensive summary for clinical toxicologists and clinical scientists.

Metformin-associated lactic acidosis reported to the United Kingdom National Poisons Information Service (NPIS) between 2010 and 2019: a ten-year retrospective analysis.

INTRODUCTION: Metformin toxicity following therapeutic use or overdose may result in metabolic acidosis with hyperlactatemia. This study aims to assess the relationship between serum lactate concentration, arterial pH, and ingested dose with severity of poisoning, and to identify if serum lactate concentration is a useful marker of severity in metformin toxicity. METHODS: A retrospective study of telephone enquiries relating to metformin exposures to the National Poisons Information Service between 2010 and 2019 from hospitals in the United Kingdom. RESULTS: Six-hundred and thirty-seven cases were identified; 117 involved metformin only and 520 involved metformin with other drugs. The majority of cases involved acute (87%) and intentional (69%) exposures. There was a statistically significant difference in doses between the Poisoning Severity Scores, as well as between intentional and unintentional or therapeutic error doses (P < 0.0001). The distribution of cases for each Poisoning Severity Score differed between the metformin only and metformin with other drugs cases (P < 0.0001). Lactic acidosis was reported in 232 cases. Serum lactate concentration and arterial pH differed across Poisoning Severity Scores. Arterial pH inversely correlated with ingested dose (r=-0.3, P = 0.003), and serum lactate concentration positively correlated with ingested dose (r = 0.37, P < 0.0001). Serum lactate concentration and arterial pH did not correlate with each other. Twenty-five deaths were recorded, all following intentional overdoses. DISCUSSION: The dataset focuses mostly on acute, intentional overdoses. Increasing ingested metformin dose, a higher serum lactate concentration and worsening arterial pH were all associated with an unfavourable Poisoning Severity Score in patients in both metformin only and metformin with other drugs groups. As serum lactate concentration did not correlate with arterial pH, it represents an independent marker of poisoning severity. CONCLUSIONS: Data from the present study suggest that serum lactate concentration can be used to assess severity of poisoning in patients who have reportedly ingested metformin.

Phenytoin and damage to the cerebellum - a systematic review of published cases.

INTRODUCTION: The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically reviewed the clinical and radiological features, and their correlation. AREAS COVERED: We identified sixty case reports and case series of the effects of phenytoin on the cerebellum by searching Medline and Embase and relevant reference lists. The reports described 92 [median 1, range 1-5] cases, documented median age 28 [2.7-78] years. Eighty-one cases described one or more clinical sign of ataxia (present in 96%), dysarthria (63%), and nystagmus (70%). The neurological outcome (in 76 cases): 10 (13%) recovered by 12 months; 55 (72%) suffered residual disability; and 11 (14%) died. Median serum phenytoin concentration (48 cases) was 50 (interquartile range 31-66) mg/L; only three values were below 20 mg/L. The radiological findings included cerebellar atrophy in 41 of 61 patients (67%) with at least one scan. EXPERT OPINION: Evidence mainly comes from case reports, and is inevitably biased. Most patients with cerebellar dysfunction have phenytoin concentrations above the reference range. Clinical signs of ataxia can persist without radiological evidence of cerebellar atrophy, and cerebellar atrophy is seen without any clinical evidence of cerebellar dysfunction.

Potential cyanide poisoning reported to the UK national poisons information service: 2008-2019.

INTRODUCTION: Cyanide is a prevalent, lethal chemical. Possible sources of exposure include products of combustion, plant material, industry, chemical warfare and terrorism. METHODS: Retrospective review of UK Poisons Information Database of telephone enquiries to the National Poisons Information Service between 1st January 2008 and 31st December 2019 where cyanide poisoning was considered a possibility. Data extracted included demographics, exposure source, clinical features, Poisoning Severity Score, lactate concentration and antidotes given. RESULTS: A total of 1,252 cases of suspected cyanide poisoning were identified, 239 (19%) involved children under 10 years. The commonest sources of exposure were ingestion of plant material (437 cases; 35%) and smoke inhalation (399; 32%). Smoke inhalation caused the majority of severe and fatal cases (139; 71%). Clinical features associated with fatal outcomes were cardiac arrest (OR 36.4; 95% CI 14.4-92.2), hypotension (15.8; 7.0-35.9), coma (10.8; 5.6-21.0) and lactic acidosis (7.8; 4.1-14.8). 110 patients (9%) were given an antidote and 40 patients (3%) died.Lactate concentrations correlate with Poisoning Severity Score category (r = 0.6, p < 0.0001). Serum lactate <2.0 mmol/L was associated with Poisoning Severity Score None or Minor (sensitivity 76%; specificity 86%) and >11.0 mmol/L was associated with fatal outcome (sensitivity 74%; specificity 80%). 61 cases (5%) had severe carboxyhaemoglobin toxicity (COHb >30%). This was associated with a fatal outcome (OR 7.0; 95% CI 1.5-33.7) and there was positive correlation between carboxyhaemoglobin and Poisoning Severity Score, r = 0.57, p < 0.0001. CONCLUSIONS: Most cases of ingestion of plant material involved children under five years and resulted in no or mild symptoms. In adults smoke inhalation was associated with the most severe poisoning. The lactate cut-off values associated with each severity score calculated in this study are lower than the values used by NPIS on TOXBASE. Analytical conformation of cyanide exposure was unavailable in the majority of case, limiting the strength of these conclusions.

Bites by exotic snakes reported to the UK National Poisons Information Service 2009-2020.

Introduction: Snakebite is recognised as a neglected tropical disease and a cause of substantial morbidity and mortality. Whilst the most medically important snakes are typically native of Asia, Africa, Latin America and Oceania, the possibility of encountering these snakes is no longer limited by geography due to an increasing number of exotic (non-native) snakes being held in captivity.Methods: A retrospective review of snakebite enquiries to the UK National Poisons Information Service (NPIS) between 2009 and 2020. Enquiries about the European adder (Vipera berus) or where the identity of the snake was unknown were excluded.Results: There were 321 exotic snakebites in 300 patients involving 68 different species during this period. Ten patients were bitten on more than one occasion. The majority of patients (64.5%) were male. Most bites were inflicted by snakes of the family Colubridae (184/321, 57.3%); seventeen bites resulted in moderate symptoms (predominantly swelling of the bitten limb). There were 30 (9.3%) bites by Viperidae and 14 (4.3%) bites by Elapidae. All severe cases (n = 15) resulted from bites by either Viperidae (n = 10) or Elapidae (n = 5). Antivenom was given in 17 cases. One fatality was recorded.Conclusions: Despite their low incidence, exotic snakebites present a substantial challenge for UK healthcare professionals. Although rare, these bites typically occur in individuals (usually male) who keep snakes as part of their occupation or hobby and are therefore at risk of multiple bites. Bites can result in venom hypersensitisation and the risk of venom-induced anaphylaxis. Rapid access to expert clinical advice is available in the UK on a 24-hour basis through the National Poisons Information Service and is strongly recommended in all cases of exotic snakebite.

Systematic Review of Human Poisoning and Toxic Exposures in Myanmar.

The International Health Regulations (2005) promote national capacity in core institutions so that countries can better detect, respond to and recover from public health emergencies. In accordance with the 'all hazards' approach to public health risk, this systematic review examines poisoning and toxic exposures in Myanmar. A systematic literature search was undertaken to find articles pertaining to poisoning in Myanmar published between 1998 and 2020. A number of poisoning risks are identified in this review, including snakebites, heavy metals, drugs of abuse, agrochemicals and traditional medicine. Patterns of poisoning presented in the literature diverge from poisoning priorities reported in other lower-middle income countries in the region. The experience of professionals working in a Yangon-based poison treatment unit also indicate that frequently observed poisoning as a result of pharmaceuticals, methanol, and petroleum products was absent from the literature. Other notable gaps in the available research include assessments of the public health burden of poisoning through self-harm, household exposures to chemicals, paediatric risk and women's occupational risk of poisoning. There is a limited amount of research available on poisoning outcomes and routes of exposure in Myanmar. Further investigation and research are warranted to provide a more complete assessment of poisoning risk and incidence.

Liquid laundry detergent capsules (PODS): a review of their composition and mechanisms of toxicity, and of the circumstances, routes, features, and management of exposure.

Introduction: Liquid laundry detergent capsules (also called single-use detergent sacs; laundry pods; laundry packets) have become an increasingly popular household product worldwide. Objectives: To review the composition and mechanisms of toxicity of liquid laundry detergent, capsules, and the circumstances, routes, clinical features (and impact of packaging changes) and management of exposure. Methods: The databases PubMed and EMBASE were searched using the terms: "detergent" and "capsule", "pod", "pac" or "sac" combined with "poison", "ingest", "expos" but not "animal" or "in vitro" or "bacteria". The searches yielded 289 articles, of which 186 were excluded: 38 duplicates, 133 not relevant, 10 abstracts which had been published as a paper and 5 non-English language articles. The bibliographies of relevant articles were hand-searched which yielded 14 additional citations. Searching of abstracts from scientific meetings produced five additional citations. A total of 122 publications were relevant to the objectives of the review. Capsules and composition: Capsules typically contain anionic surfactants (20-35%), non-ionic surfactants (10-20%), propylene glycol (8-20%) and ethanol (2-5%) within a water-soluble polyvinyl alcohol membrane. Mechanisms of toxicity: Non-ionic surfactants are the primary mechanism, though anionic surfactants, ethanol and propylene glycol may also contribute. Circumstances of exposure: The majority (60%) of children are exposed when the capsule is removed from its original container. Routes of exposure: Ingestion is the most common (>85%); ocular (<15%) and dermal (<8%) exposure account for the remainder. Features following ingestion: Features develop in around half of all exposures, though >90% are minor. In those with features, vomiting occurs in some 50%; coughing and drowsiness are reported in <5%. Respiratory depression (<0.5%), central nervous system depression (<0.1%) esophageal or gastric injury (<0.5%), metabolic acidosis and hyperlactatemia (<0.05%) have been reported rarely. Of 17 deaths reported, 13 were adults and nine were suffering from cognitive impairment. Features following ocular exposure: Conjunctivitis, eye irritation and/or eye pain are commonly experienced; corneal injury is less common but complete recovery typically occurs within one week. Features following dermal exposure: Clinically important dermal toxicity seldom occurs, though skin burns can develop in <5% of cases when skin contact is prolonged. Impact of packaging changes on features: The implementation of packaging changes resulted in a fall in the number of exposures and their severity in the United States and in the number in Italy. Management-ingestion: Gut decontamination is not recommended, though small amounts of fluid can be administered orally to rinse out the mouth. Symptomatic and supportive care should be offered to all patients that develop features of toxicity. Supplemental oxygen should be administered for hypoxemia, and bronchodilators for laryngospasm/bronchospasm. Intubation and assisted ventilation may be required if CNS and respiratory depression develop. A chest radiograph should be performed if respiratory features develop. In patients with swallowing difficulties, drooling or oropharyngeal burns, endoscopy should be performed; if substantial mucosal damage is present MRI should be considered. In addition, intravenous fluids will be required if prolonged vomiting or diarrhea occur and acid-base disturbances should be corrected. Management-eye exposure: Thorough irrigation of the eye with sodium chloride 0.9% is required. Instillation of a local anesthetic will reduce discomfort and help more thorough decontamination. Due to the potential for corneal injury, fluorescein should be instilled. If ocular injury is present, the patient should be referred to an ophthalmologist. Management-skin exposure: Skin should be irrigated thoroughly with soap and water, and burns should be treated as a thermal burn. Conclusions: Accidental ingestion usually produces no or only minor features. Very rarely respiratory depression, central nervous system depression, esophageal or gastric injury, hyperlactatemia and metabolic acidosis occur. Ocular exposure results in corneal injury infrequently and skin burns can develop uncommonly following prolonged dermal contact. Of 17 deaths reported, 13 were adults and nine were suffering from cognitive impairment.

A review of 4652 exposures to liquid laundry detergent capsules reported to the United Kingdom National Poisons Information Service 2008-2018.

Introduction: Liquid laundry detergent capsules contain concentrated liquid laundry detergent in a water-soluble polyvinyl alcohol membrane.Objective: To review 4652 exposures reported to the United Kingdom National Poisons Information Service (NPIS) and to assess the impact of regulatory changes on potential toxicity.Methods: Telephone enquiries to the NPIS and returned questionnaires for these products were analyzed for the period January 2008 to December 2018.Results: Data on 4652 exposures were reported by telephone or questionnaire, of which 95.4% involved children aged ≤5 years. Overall, 1738 of 4594 patients remained asymptomatic (Poisoning Severity Score [PSS] 0), 2729 developed minor (PSS 1) features, 107 suffered moderate features (PSS 2), 19 were graded as severe (PSS 3) and one died. Ingestion was involved in most exposures (n = 4175): vomiting occurred in 46.5%, coughing occurred in 4.3% and central nervous system depression in 3.2%. Nine (0.2%) children were intubated and ventilated. The eye was exposed in 646 cases: 371 (59.8%) suffered conjunctivitis or eye irritation and 21 (3.4%) had keratitis/corneal damage, which persisted in one patient for 9 d. The skin was involved in 364 cases; in 127 (35.5%) minor dermal features developed including erythema, irritation and rash. The most commonly reported features in the 127 cases with PSS ≥2 were vomiting (n = 75), stridor (n = 34), CNS depression (n = 22), keratitis/corneal damage (n = 21), coughing (n = 18), conjunctivitis (n = 13), hypersalivation (n = 12), foaming from the mouth (n = 11) and hypoxemia (n = 11). However, respiratory features (stridor, hypoxemia, bronchospasm, respiratory distress, dyspnea, pulmonary aspiration and tachypnea) were the reason for grading 56 of 127 cases as PSS ≥2.Conclusions: This large data set of 4652 exposures is reassuring in that 97.2% of exposures resulted in no or only minor features, only 107 patients suffered moderate features (PSS 2) and 19 severe (PSS 3) features; one patient died.

Exposures to automatic dishwashing rinse aids reported to the United Kingdom National Poisons Information Service 2008-2016.

OBJECTIVE: To determine the toxicity of rinse aids which are used as drying aids to remove water from crockery. METHODS: Enquiries to the UK National Poisons Information Service (NPIS) were analysed retrospectively for the period January 2008 to December 2016. RESULTS: There were 855 enquiries relating to 828 patients; children aged 5 years or less accounted for 91.1%. Most exposures occurred from ingestion alone (n = 778, 94.0%), but 26 involved ingestion and other routes: 21 with skin contact, 3 with eye contact, and two with both skin and eye contact. There were a further 24 cases of eye contact alone (n = 20, 2.4%) or skin contact alone (n = 3, 0.4%) and a single case of inhalation alone. The World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists (WHO/IPCS/EC/EAPCCT) Poisoning severity score [PSS] was known in 824 of the 828 exposures: 425 of 824 (51.6%) patients did not develop clinical features, 381 (46.2%) had a PSS of 1 (minor toxicity), 15 (1.8%) developed moderate (PSS 2) and 3 (0.4%) severe (PSS 3) toxicity. Vomiting was the most common feature, occurring in over a third of all ingestions (n = 286, 35.8%), followed by coughing (n = 73, 9.1%). A higher proportion of adults than children developed clinical features (72.7% of 33 vs 46.0% of 767, p = .0026), although vomiting occurred significantly more frequently amongst children (p = .0315). Of the 25 eye contact cases, eye pain (n = 8) and/or eye irritation (n = 8) were reported, with or without abnormal vision (n = 7); there were two cases of corneal abrasion. Dermal contact rarely produced features; only 4 of 26 patients reported symptoms including skin rash or burning or numbness at the contact site. CONCLUSIONS: Severe clinical features were uncommon following rinse aid exposure; vomiting was the most frequently reported symptom following ingestion.

Iron overdose epidemiology, clinical features and iron concentration-effect relationships: the UK experience 2008-2017.

Background: Iron poisoning is potentially serious, but mortality has fallen worldwide since implementation of pack size and packaging restrictions, and changes in iron use during pregnancy. The management of individual cases of overdose remains problematic due to uncertainty about indications for antidote. We examine the epidemiology of iron overdose in hospital cases referred to the UK National Poisons Information Service (NPIS) and evaluate the toxicokinetics of iron in patients ingesting only iron preparations. Methods: Anonymized hospital referral patient data from the NPIS database were collated for the period 1 January 2008 to 31 July 2017. Information was extracted, where recorded, on type of ingestion [iron alone (single), or combined with other agents (mixed)], reported dose, iron salt, timed iron concentrations and symptoms. In single-agent ingestions, the relationships between reported elemental iron dose, early concentrations (4-6 h), and symptoms were evaluated in teenagers and adults (≥13 years) and children (≤12 years) using standard statistical techniques (correlation and unpaired nonparametric comparisons). In those patients with sufficient sample points (three or more), a simple kinetic analysis was conducted. Results: Of 2708 patients with iron overdoses referred by UK hospitals for advice during the 9.7 years study period, 1839 were single-agent ingestions. There were two peaks in age incidence in single-agent exposures; 539/1839 (28.4%) were <6 years (54.1% males) while 675/1839 (36.7%) were between 13 and 20 years (91% females), the latter a substantial excess over the proportion in the totality of hospital referrals to the NPIS in the same period (13-20 years: 23,776/144,268 16.5%; 67.5% female) (p < .0001 overall and for female %). In 475 teenagers and adults and 86 children, with at least one-timed iron concentration available, there was no correlation between stated dose and iron concentration measured 4-6 h post-ingestion. Observed peak iron concentrations were not related to reported symptoms in adults. Initial iron concentrations were significantly higher in 30 patients (25 adults, 5 children) who received desferrioxamine (DFO) compared to those that did not [no DFO: mean 63.8 µmol/L (95% CI 62.1-65.6), median 64; DFO: mean 78.5 µmol/L (95% CI 69.2-87.7), median 78.1; Mann-Whitney p < .0018). No significant differences in symptoms were observed pre-treatment between DFO-treated and untreated groups. No patients died in this cohort. Conclusion: Single-agent iron exposures reported from UK hospitals were most common in children <5 years and young people aged 13-20 years. Poisoning with organ failure was not identified and there were no fatalities. No correlations were observed between reported iron doses and early concentrations, or between iron concentrations and symptoms in this cohort of mild-to-moderate poisoning.

11 analytically confirmed cases of mexedrone use among polydrug users.

INTRODUCTION: Mexedrone, 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one, is the alpha-methoxy-derivative of mephedrone (4-methyl-N-methyl cathinone). Mexedrone inhibits the re-uptake of serotonin and dopamine in a dose-dependent manner and has affinity for serotonin and dopamine membrane transporters and receptors (5-HT2 and D2 receptors), producing sympathomimetic effects similar to amfetamines. To date there are no published clinical reports on mexedrone use that are analytically confirmed. OBJECTIVE: To characterise the features of mexedrone use in patients who presented to our hospital after using a variety of psychoactive substances including mexedrone, with analytical confirmation in each case. METHODS: This is an observational case series. Urine toxicological screening using ultra-performance liquid chromatography with tandem mass spectrometry and exact mass time of flight was employed in all patients. RESULTS: A total of 305 cases were screened and mexedrone was identified in 11 urine samples. Agitation was the most common presenting feature in 10 of 11 patients. This was marked to the extent of aggression in some cases, with six patients requiring sedation and/or physical restraint. Delusions and hallucinations, often with paranoia, were observed in three cases with a prominent supernatural/demonic theme. None of these individuals had a history of psychosis. Seven of 11 patients were tachycardic >100 bpm. The median length of stay was 20 hours (range 2-77; IQR 4-33). Mexedrone alone is only likely to have been responsible for these clinical features in 2 cases; in two others mexedrone was found in high concentration along with substantial amounts of other stimulants. In 7 other cases other stimulants detected more likely explained the features. However, comprehensive analytical data enabled us to identify the full complement of agents contributing to the clinical presentation. CONCLUSIONS: Agitation was the predominant clinical feature in this case series and was often accompanied by a sinus tachycardia; mexedrone was primarily responsible in 2 patients but contributed substantially in two others. Patients typically recovered fully within 24 hours, unless they required sedation.

Toxicity from automotive screenwashes reported to the United Kingdom National Poisons Information Service (NPIS) from 2012 to 2015.

BACKGROUND: Automotive screenwashes commonly contain ethylene glycol, methanol, and/or isopropanol; ethanol is also included in many formulations. The concentrations and combinations of each constituent vary considerably between the products. This study was undertaken to investigate the toxicity of automotive screenwashes as reported by telephone to the United Kingdom National Poisons Information Service (NPIS). METHODS: Enquiries to the NPIS relating to automotive screenwashes were analyzed retrospectively for the period January 2012 to December 2015. RESULTS: There were 295 enquiries involving 255 individual exposures. The majority (n = 241, 94.5%) of exposures involved ingestion and 14 of these also involved other routes. Six cases were due to skin contact alone, three to inhalation alone, three to eye contact alone, one to ear exposure alone and another occurred from inhalation and skin contact. Children below 5 years of age accounted for 26% of all ingestions. The identity (and therefore composition) of the screenwash was known with certainty in 124 of 241 ingestions and included methanol in 106 formulations, isopropanol in 72, ethylene glycol in 38, and ethanol in 104. The World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score was known in 235 of 241 cases of ingestion: most patients were asymptomatic (n = 169, 71.9%), but 59 (25.1%) developed minor (PSS 1), six (2.6%) moderate (PSS 2), and one patient severe (PSS 3) features; this patient later died. Nausea (n = 10), vomiting (n = 11), abdominal pain (n = 10), metabolic acidosis (n = 8) and raised anion gap (n = 8) were reported most commonly after ingestion. CONCLUSIONS: Most patients (71.9%) ingesting automotive screenwash did not develop features. The implication is that the amount of screenwash ingested was very small. Skin and eye exposure produced either no features or only minor toxicity.

Toxicity from fluoropolymer-containing grout, tile and stone floor sealants reported to the UK National Poisons Information Service 2009-2015.

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.

Toxicity resulting from exposure to oven cleaners as reported to the UK National Poisons Information Service (NPIS) from 2009 to 2015.

INTRODUCTION: Oven cleaning products contain corrosive substances, typically sodium or potassium hydroxide. OBJECTIVE: To determine the reported toxicity from exposure to oven cleaning products. METHODS: Telephone enquiries to the UK National Poisons Information Service regarding oven cleaning products were analysed retrospectively for the period January 2009 to December 2015. RESULTS: There were 796 enquiries relating to 780 patients. Ninety-six percent of the products involved in the reported exposures contained sodium hydroxide and/or potassium hydroxide. Ingestion alone (n = 285) or skin contact alone (n = 208) accounted for the majority of cases; inhalation alone (n = 101), eye contact alone (n = 97), and multiple routes of exposure (n = 89) accounted for the remainder. Ninety-five percent of patients exposed by inhalation, 94% exposed dermally and 85% reporting eye exposure, developed features of toxicity. Patients exposed by multiple routes developed symptoms in 70% of cases. Only 103 of the 285 patients ingested oven cleaner directly, whereas 182 patients ingested food they considered to have been contaminated with oven cleaner. In 100 of the 103 direct ingestions where the features and World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score were known, 56 reported symptoms which were minor in 51 cases. The most common features following ingestion were vomiting (n = 26), abdominal pain (n = 22) or pharyngitis (n = 15). Skin burns (n = 91) predominantly involving the hands or arms, occurred in 44% of dermal exposures. Following inhalation, patients frequently developed respiratory features (n = 52) including coughing and chest pain/tightness. Eye pain (n = 43) and conjunctivitis (n = 33) commonly occurred following ocular exposure. CONCLUSIONS: Most (71%) patients exposed to an oven cleaner irrespective of the route of exposure developed features of toxicity, though in most cases only minor features developed; moderate or severe features ensued in ∼4%. Those patients exposed dermally, ophthalmically or by inhalation developed features more frequently (≥85%) than those who ingested a product directly (56%).

Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.

CONTEXT: Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. MATERIALS AND METHODS: We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations. RESULTS: Pre-chelation blood lead concentrations ranged between 99 and 150 µg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others. CONCLUSIONS: Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

Sodium fluoroacetate poisoning.

Sodium fluoroacetate was introduced as a rodenticide in the US in 1946. However, its considerable efficacy against target species is offset by comparable toxicity to other mammals and, to a lesser extent, birds and its use as a general rodenticide was therefore severely curtailed by 1990. Currently, sodium fluoroacetate is licensed in the US for use against coyotes, which prey on sheep and goats, and in Australia and New Zealand to kill unwanted introduced species. The extreme toxicity of fluoroacetate to mammals and insects stems from its similarity to acetate, which has a pivotal role in cellular metabolism. Fluoroacetate combines with coenzyme A (CoA-SH) to form fluoroacetyl CoA, which can substitute for acetyl CoA in the tricarboxylic acid cycle and reacts with citrate synthase to produce fluorocitrate, a metabolite of which then binds very tightly to aconitase, thereby halting the cycle. Many of the features of fluoroacetate poisoning are, therefore, largely direct and indirect consequences of impaired oxidative metabolism. Energy production is reduced and intermediates of the tricarboxylic acid cycle subsequent to citrate are depleted. Among these is oxoglutarate, a precursor of glutamate, which is not only an excitatory neurotransmitter in the CNS but is also required for efficient removal of ammonia via the urea cycle. Increased ammonia concentrations may contribute to the incidence of seizures. Glutamate is also required for glutamine synthesis and glutamine depletion has been observed in the brain of fluoroacetate-poisoned rodents. Reduced cellular oxidative metabolism contributes to a lactic acidosis. Inability to oxidise fatty acids via the tricarboxylic acid cycle leads to ketone body accumulation and worsening acidosis. Adenosine triphosphate (ATP) depletion results in inhibition of high energy-consuming reactions such as gluconeogenesis. Fluoroacetate poisoning is associated with citrate accumulation in several tissues, including the brain. Fluoride liberated from fluoroacetate, citrate and fluorocitrate are calcium chelators and there are both animal and clinical data to support hypocalcaemia as a mechanism of fluoroacetate toxicity. However, the available evidence suggests the fluoride component does not contribute. Acute poisoning with sodium fluoroacetate is uncommon. Ingestion is the major route by which poisoning occurs. Nausea, vomiting and abdominal pain are common within 1 hour of ingestion. Sweating, apprehension, confusion and agitation follow. Both supraventricular and ventricular arrhythmias have been reported and nonspecific ST- and T-wave changes are common, the QTc may be prolonged and hypotension may develop. Seizures are the main neurological feature. Coma may persist for several days. Although several possible antidotes have been investigated, they are of unproven value in humans. The immediate, and probably only, management of fluoroacetate poisoning is therefore supportive, including the correction of hypocalcaemia.

Management of poisoning with ethylene glycol and methanol in the UK: a prospective study conducted by the National Poisons Information Service (NPIS).

BACKGROUND: Poisoning with methanol and ethylene glycol can cause serious morbidity and mortality. Specific treatment involves the use of antidotes (fomepizole or ethanol) with or without extracorporeal elimination techniques. METHODS: A prospective audit of patients with methanol or ethylene glycol poisoning reported by telephone to the National Poisons Information Service (NPIS) in the UK was conducted during the 2010 calendar year and repeated during the 2012 calendar year. The study was conducted to determine the frequency of clinically significant systemic toxicity and requirement for antidote use and to compare outcomes and rates of adverse reaction and other problems in use between ethanol and fomepizole. RESULTS: The NPIS received 1315 enquiries involving methanol or ethylene glycol, relating to 1070 individual exposures over the 2-year period. Of the 548 enquiries originating from hospitals, 329 involved systemic exposures (enteral or parenteral as opposed to topical exposure), of which 216 (66%) received an antidote (204 for ethylene glycol and 12 for methanol), and 90 (27%) extracorporeal treatment (86 for ethylene glycol and 4 for methanol). Comparing ethanol with fomepizole, adverse reactions (16/131 vs. 2/125, p < 0.001) and administration errors, lack of monitoring, or inappropriate use (45/131 vs. 6/125, p < 0.0001) were reported more commonly, whereas non-availability and inadequate stocks were reported less commonly (6/125 vs. 33/131, p < 0.0001). Eight fatalities and complications or sequelae occurred in 21 patients. Poor outcome (death, complications, or sequelae) was significantly associated with older age, higher poisoning severity scores, and lower pH on admission (p < 0.001). CONCLUSIONS: Systemic poisoning with ethylene glycol or methanol results in hospitalisation at least 2-3 times per week on average in the UK. No difference in outcome was detected between ethanol and fomepizole-treated patients, but ethanol was associated with more frequent adverse reactions.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.

CONTEXT: No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning. OBJECTIVE: Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model. MATERIAL AND METHODS: This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies. RESULTS: The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability. CONCLUSIONS: A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.