Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service.

AIMS: Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). METHODS: NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. RESULTS: Of 22 937 patient-specific telephone enquiries, 10 398 did not involve co-ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. CONCLUSIONS: Mefenamic acid overdose is associated with a much larger and dose-related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit-risk profile of mefenamic acid should now be re-evaluated in light of effective and less toxic alternatives.

Methoxetamine toxicity reported to the National Poisons Information Service: clinical characteristics and patterns of enquiries (including the period of the introduction of the UK's first Temporary Class Drug Order).

OBJECTIVE: To report the demographic and clinical characteristics of cases of methoxetamine toxicity reported to The National Poisons Information Service (NPIS) by healthcare professionals. To assess the pattern of enquiries from health professionals to the UK NPIS related to methoxetamine, including the period of the making of the UK first Temporary Class Drug Order (TCDO). METHODS: All telephone enquiries to and user sessions for TOXBASE, the NPIS on-line information resource, related to methoxetamine (and synonyms 'MXE', 'mket' and '2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone') were reviewed from 1 April 2010 to 1 August 2012. Data were compared for the 3 months before and after the TCDO. RESULTS: There were 47 telephone enquiries and 298 TOXBASE sessions regarding methoxetamine during the period of study. Comparing the 3 months before and after the TCDO, TOXBASE sessions for methoxetamine fell by 79% (from 151 to 32) and telephone enquiries by 80% (from 15 to 3). Clinical features reported by enquirers were consistent with case reports of analytically confirmed methoxetamine toxicity and typical toxidromes were of stimulant (36%), reduced consciousness (17%), dissociative (11%) and cerebellar (6.4%) types, but also particularly featured acute disturbances in mental heath (43%). CONCLUSIONS: Structured NPIS data may reveal trends in drugs of abuse use and toxicity when interpreted within their limitations. Since April 2012, there have been fewer enquiries to NPIS from clinicians, indicating reduced presentations with suspected methoxetamine toxicity to healthcare services. It is unclear if this is related to the TCDO made on 5 April 2012.

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.

The clinical toxicology of sodium hypochlorite.

INTRODUCTION: Sodium hypochlorite is used as a bleaching and disinfecting agent and is commonly found in household bleach. OBJECTIVE: The objective is to review critically the epidemiology, mechanisms of toxicity, clinical features, diagnosis, and management of hypochlorite poisoning. METHODS: PubMed was searched from January 1950 to June 2018 using the terms "Hypochlorite", "Sodium Hypochlorite", "Sodium Oxychloride", "Hypochlorous Acid", "Bleach", "Chlorine Bleach", in combination with the keywords "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". In addition, bibliographies of identified articles were screened for additional relevant studies including non-indexed reports. Non-peer-reviewed sources were also included. These searches produced 110 citations which were considered relevant. EPIDEMIOLOGY: There is limited information regarding statistical trends on world-wide poisoning from sodium hypochlorite. In the United States of America, poison control center data have shown that enquiries regarding hypochlorite bleaches have ranged from 43,000 to 46,000 per year over the period 2012-2016. Mechanisms of toxicity: Hypochlorite's potential to cause toxicity is related to its oxidizing capacity and the pH of the solution. Toxicity arises from its corrosive activity upon contact with mucous membranes and skin. Features following ingestion: While small accidental ingestions are very unlikely to cause clinically significant toxicity, large ingestions may cause corrosive gastrointestinal injury and systemic effects, including metabolic acidosis, hypernatremia, and hyperchloremia. Features following dental exposure: Hypochlorite is used extensively by dentists for cleaning root canals and is safe if the solution remains within the root canal. Extrusions into the periapical area can result in severe pain with localized large and diffuse swelling and hemorrhage. Features following skin exposure: Prolonged or extensive exposure may cause skin irritation and damage to the skin or dermal hypersensitivity. Such exposures can result in either immediate or delayed-type skin reactions. High concentration solutions have caused severe chemical skin burns. Features following inhalation: Although there are only limited data, inhalation of hypochlorite alone is likely to lead to no more than mild irritation of the upper airways. Features following ocular exposure: Corneal injuries from ocular exposure are generally mild with burning discomfort and superficial disturbance of the corneal epithelium with recovery within 1 or 2 days. With higher concentration solutions, severe eye irritation can occur. DIAGNOSIS: The diagnosis can typically be made on the basis of a careful history, including details of the specific product used, its hypochlorite concentration, and the amount involved. As hypochlorite bleach produces a characteristic smell of chlorine, this may provide a diagnostic clue. In severe cases, corrosive injury is suggested on presentation because of hypersalivation, difficulty swallowing, retrosternal pain or hematemesis. MANAGEMENT: Symptom-directed supportive care is the mainstay of management. Gastrointestinal decontamination is not beneficial. Local corrosive injury is the major focus of treatment in severe cases. Fiberoptic endoscopy and CT thorax/abdomen are complimentary and have been shown to be useful in corrosive injuries in assessing the severity of injury, risk of mortality and risk of subsequent stricture formation and should be performed as soon as possible after ingestion. Dental periapical extrusion injuries should be left open for some minutes to allow bleeding through the tooth and to limit hematoma development in tissue spaces. Once the bleeding has ceased, the canal can be dressed with non-setting calcium hydroxide and sealed coronally. CONCLUSIONS: Accidental ingestion of household bleach is not normally of clinical significance. However, those who ingest a large amount of a dilute formulation or a high concentration preparation can develop severe, and rarely fatal, corrosive injury so prompt supportive care is essential as there is no specific antidote. Treatment primarily consists of symptom-directed supportive care.

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.

Winston Churchill (1874-1965), Dr Robson Roose, MD Brux, FRCPE (1848-1905) and Dr Joseph Rutter, MD Lond, MRCP (1834-1913): Treatment for pneumonia in March 1886.

This paper will review Winston Churchill's severe respiratory illness in March 1886 when he developed pneumonia of the right lung as an 11-year-old boy. Winston was treated supportively with 'nourishment, stimulants [probably alcohol] and close watching' at his school by the 'celebrated' family physician, Dr Robson Roose, with the assistance of Dr Joseph Rutter. Roose was exemplary in his commitment to his young patient and assiduous in informing Lord Randolph Churchill of his son's clinical progress by letter.

Did Winston Churchill suffer a myocardial infarction in the White House at Christmas 1941?

While staying in the White House over Christmas 1941, Churchill developed chest pain on trying to open a window in his bedroom. Sir Charles Wilson, his personal physician, diagnosed a 'heart attack' (myocardial infarction). Wilson, for political and personal reasons, decided not to inform his patient of the diagnosis or obtain assistance from US medical colleagues. On Churchill's return to London, Wilson sought a second opinion from Dr John Parkinson who did not support the diagnosis of coronary thrombosis (myocardial infarction) and reassured Churchill accordingly.

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.

Exposures to traditional automatic dishwashing tablets and a comparison with exposures to soluble film tablets reported to the United Kingdom National Poisons Information Service 2008-2015.

INTRODUCTION: Traditional automatic dishwashing tablets are contained within an external wrapper that requires removal prior to use. OBJECTIVE: To determine the toxicity of traditional tablets and to compare this with our previously reported experience of soluble film dishwashing tablets. METHODS: Telephone enquiries regarding traditional tablets were analysed retrospectively for the period January 2008 to December 2015. RESULTS: Traditional tablets: There were 503 enquiries relating to 492 patients who had been exposed to a traditional tablet. Most involved children aged 5 years or less (87.4%). The majority (78.6%) of patients did not develop symptoms after exposure; 21.1% developed minor (PSS 1) symptoms while one patient developed moderate features. Exposure occurred predominantly as a result of ingestion (n = 476, 96.7%); the most common feature in symptomatic patients (n = 99, 20.8%) was vomiting (70 [14.7%] cases). Significantly (p < 0.0001) more adults (44.9% of 49 adults; 95% CI = 31.9-58.7) were reported with features than children (18.2% of 434; 95% CI = 14.9-22.1). There were five cases of eye contact which resulted in eye pain in two patients and eye irritation in another. Only one of 11 patients exposed dermally developed features (a rash around the mouth). Comparison with soluble film exposures: The percentage of patients that were reported with clinical symptoms following ingestion of a soluble film dishwashing tablet (31.7% of 473 patients; 95% CI = 27.7-36.0) was significantly greater (p < 0.0001) than that for a traditional tablet (20.9% of 483 patients; 95% CI = 17.5-24.8). Vomiting was the most commonly reported feature and occurred significantly (p < 0.0001) more frequently amongst patients who had ingested a soluble film tablet (25.5%; 95% CI = 21.8-29.6) than a traditional tablet (14.7%; 95% CI = 11.8-18.1). CONCLUSIONS: Exposure to both traditional and soluble film tablets only rarely produced clinically significant symptoms (PSS ≥2). However, ingestion of a soluble film tablet was significantly more likely to result in clinical features than ingestion of a traditional tablet.

The impact of an international initiative on exposures to liquid laundry detergent capsules reported to the United Kingdom National Poisons Information Service between 2008 and 2015.

INTRODUCTION: Although the majority of those exposed to liquid laundry detergent capsules remain asymptomatic or suffer only minor clinical features after exposure, a small proportion develop central nervous system depression, stridor, pulmonary aspiration and/or airway burns following ingestion or conjunctivitis and corneal ulceration following eye exposure. As a consequence, the International Association for Soaps, Detergents and Maintenance Products (AISE) established a Product Stewardship Programme in Europe, requiring that safety measures be implemented to reduce the visibility of, and restrict access to, these detergent capsules by small children. Implementation occurred in the United Kingdom over several months during the first half of 2013. OBJECTIVE: This study investigated whether the AISE Programme had an impact on the number and severity of exposures reported to the United Kingdom National Poisons Information Service. METHODS: Telephone enquiries to the National Poisons Information Service relating to liquid laundry detergent capsules were analysed for the period January 2008 to December 2015. RESULTS: While there was a significant difference (p = 0.0002) between the mean number of annual exposures (469.4) reported between 2008 and 2012 and the mean number reported between 2014 and 2015 (403.5), the number of exposures was decreasing steadily prior to implementation of the Programme in 2013, which did not impact this fall from 2013 onwards. In addition, the number of exposures per million units sold was not impacted by the Programme. There was no significant difference (p = 0.68) between the mean number of exposures (11.8) with PSS ≥2 reported between 2008 and 2012 and the mean number (13.0) reported between 2014 and 2015. Although there was a 28.7% decrease between 2010-2012 and 2014-2015 in the number of exposures with PSS ≥2 per million units sold, this decrease was not statistically significant (p = 0.18). CONCLUSION: There is no evidence that the Product Stewardship Programme had a beneficial impact on the number of exposures reported to the National Poisons Information Service or their severity.

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.

The role of oximes in the treatment of nerve agent poisoning in civilian casualties.

There are important differences between on-target military attacks against relatively well protected Armed Forces and nerve agent attacks initiated by terrorists against a civilian population. In contrast to military personnel, civilians are unlikely to be pre-treated with pyridostigmine and protected by personal protective equipment. Furthermore, the time after exposure when specific therapy can first be administered to civilians is likely to be delayed. Even conservative estimates suggest a delay between exposure and the first administration of atropine/oxime of at least 30 minutes. The organophosphorus nerve agents are related chemically to organophosphorus insecticides and have a similar mechanism of toxicity, but a much higher mammalian acute toxicity, particularly via the dermal route. Nerve agents phosphonylate a serine hydroxyl group in the active site of the enzyme, acetylcholinesterase (AChE), which results in accumulation of acetylcholine and, in turn, causes enhancement and prolongation of cholinergic effects and depolarisation blockade. The rate of spontaneous reactivation of AChE is variable, which partly accounts for differences in acute toxicity between the nerve agents. With soman in particular, an additional reaction occurs known as 'aging'. This consists of monodealkylation of the dialkylphosphonyl enzyme, which is then resistant to spontaneous hydrolysis and reactivation by oximes. Monodealkylation occurs to some extent with all dialkylphosphonylated AChE complexes; however, in general, is only of clinical importance in relation to the treatment of soman poisoning, where it is a very serious problem. With soman, aging occurs so fast that no clinically relevant spontaneous reactivation of AChE occurs before aging has taken place. Hence, recovery of function depends on resynthesis of AChE. As a result, it is important that an oxime is administered as soon after soman exposure as possible so that some reactivation of AChE occurs before all the enzyme becomes aged. Even though aging occurs more slowly and reactivation occurs relatively rapidly in the case of nerve agents other than soman, early oxime administration is still clinically important in patients poisoned with these agents. Experimental studies on the treatment of nerve agent poisoning have to be interpreted with caution. Some studies have used prophylactic protocols, whereas the drugs concerned (atropine, oxime, diazepam) would only be given to a civilian population after exposure. The experimental use of pyridostigmine before nerve agent exposure, although rational, is not of relevance in the civilian context. With the possible exception of the treatment of cyclosarin (GF) and soman poisoning, when HI-6 might be preferred, a review of available experimental evidence suggests that there are no clinically important differences between pralidoxime, obidoxime and HI-6 in the treatment of nerve agent poisoning, if studies employing pre-treatment with pyridostigmine are excluded.

Severe and fatal pharmaceutical poisoning in young children in the UK.

OBJECTIVE: Accidental poisoning in young children is common, but severe or fatal events are rare. This study was performed to identify the number of such events occurring in the UK and the medications that were most commonly responsible. DESIGN: Analysis of national data sets containing information relating to severe and fatal poisoning in children in the UK. DATA SOURCES: Office of National Statistics mortality data for fatal poisoning; Paediatric Intensive Care Audit Network admissions database and the National Poisons Information Service for severe non-fatal poisoning; Hospital Episode Statistics for admission data for implicated agents. RESULTS: Between 2001 and 2013, there were 28 children aged 4 years and under with a death registered as due to accidental poisoning by a pharmaceutical product in England and Wales. Methadone was the responsible drug in 16 (57%) cases. In the UK, 201 children aged 4 years and under were admitted to paediatric intensive care with pharmaceutical poisoning between 2002 and 2012. The agent(s) responsible was identified in 115 cases, most commonly benzodiazepines (22/115, 19%) and methadone (20/115, 17%). CONCLUSIONS: Methadone is the most common pharmaceutical causing fatal poisoning and a common cause of intensive care unit admissions in young children in the UK.

Toxicity of soluble film automatic dishwashing products as reported to the United Kingdom National Poisons Information Service 2008-2015.

INTRODUCTION: Soluble film automatic dishwashing tablets, unlike their traditional counterparts, require no removal from an outer protective wrapper prior to use. Instead, the tablets are enclosed by a water-soluble polyvinyl alcohol film and are loaded straight into the dishwashing machine. They most commonly contain a source of hydrogen peroxide (often as sodium percarbonate) and non-ionic surfactants. Other constituents in some formulations include sodium carbonate, sodium tripolyphosphate and sodium silicate, which reduce water hardness. The pH once dissolved in water is alkaline. OBJECTIVE: To determine the toxicity from exposure to soluble film automatic dishwashing tablets. METHODS: Telephone enquiries to the United Kingdom National Poisons Information Service regarding soluble film automatic dishwashing products were analysed retrospectively for the period January 2008 to December 2015. RESULTS: There were 498 enquiries relating to 488 patients. Almost all exposures occurred in the home (98.4%) and involved children aged ≤5 years (92.8%). Exposure occurred mainly as a result of ingestion alone (n = 470, 96.3%); eye contact alone (n = 9, 1.8%) and exposures involving multiple routes (ingestion with skin or eye contact; n = 9, 1.8%) made up the remaining cases. The majority of patients were asymptomatic following exposure (n = 325, 67.4%). The most common feature following ingestion was vomiting which occurred in 121 of 474 cases (25.5%) where clinical data were available. Nausea (n = 8, 1.7%) and coughing (n = 6, 1.3%) were also reported; three patients developed stomatitis and another five developed a rash where ingestion alone was considered to be the sole route of exposure. Ocular exposure to the tablet contents resulted in blurred vision, eye pain or conjunctivitis in seven of ten patients. CONCLUSION: Ingestion of a soluble film automatic dishwashing tablet rarely resulted in clinically significant symptoms, which is surprising given the potential hazard of the ingredients. Hence, it seems probable that the amount of material actually ingested was very small or that most was spat out.