Increasing frequency of severe clinical toxicity after use of 2,4-dinitrophenol in the UK: a report from the National Poisons Information Service.

OBJECTIVE: 2,4-Dinitrophenol (DNP) increases energy consumption by uncoupling oxidative phosphorylation. Although not licensed as a medicine, it is sometimes used by 'body sculptors' and for weight loss as a 'fat burning' agent. This research was performed to characterise patterns of presentation, clinical features and outcomes of patients reported to the National Poisons Information Service (NPIS) in the UK after exposure to DNP. METHODS: NPIS telephone enquiry records and user sessions for TOXBASE, the NPIS online information database, related to DNP, were reviewed from 1 January 2007 to 31 December 2013. RESULTS: Of the 30 separate systemic exposures to DNP reported by telephone to NPIS during the study period (27 males, 3 females, with a median age of 23.5 years), there were 3 during 2007-2011 (inclusive), 5 during 2012 and 22 during 2013. TOXBASE user sessions also increased sharply from 6 in 2011 to 35 in 2012 and 331 in 2013. The modes of exposure reported in telephone enquiries were chronic (n=2), acute (n=12) and subacute (n=16). Commonly reported clinical features were fever (47%), tachycardia (43%), sweating (37%), nausea or vomiting (27%), skin discolouration or rash (23%), breathing difficulties (23%), abdominal pain (23%), agitation (13%) and headache (13%). There were five (17%, 95% CI 6.9% to 34%) fatalities, four involving acute overdose. CONCLUSIONS: The study indicates a substantial recent increase in clinical presentations with toxicity caused by exposure to DNP in the UK with an associated high mortality. Further steps are needed to warn potential users of the severe and sometimes fatal toxicity that may occur after exposure to this compound.

Snakebite enquiries to the UK National Poisons Information Service: 2004-2010.

OBJECTIVE: To describe trends regarding snakebite enquiries to the UK National Poisons Information Service (NPIS) from 2004 to 2010. METHODS: The NPIS telephone enquiry database, the UK Poisons Information Database, was interrogated for enquiries to the four NPIS units from 2004 to 2010. Search terms used were 'snake' and 'snakebite'. Information from the national dataset was available from Cardiff and Edinburgh units from 2004 onwards, Birmingham from June 2005 and Newcastle from September 2006. RESULTS: Five hundred and ten cases were identified, of which 69% were male and 31% female. Average age of cases was 32 years (±1 95% CI). The snake was identified as follows: British Adder in 52% of cases, an exotic species in 26%, unknown in 18% and another UK snake in 4%. 82% of cases occurred between the months of April and September. Cases peaked during August (19%). Forty-two per cent of enquiries involved features of envenoming. Eighty-five cases were assessed as requiring antivenom. Eighty-four cases received treatment with antivenom. No adverse reactions to the antivenom were reported and resolution of clinical features was reported in all treated cases. Advice to use an antidote was followed in 98.8% of cases. CONCLUSIONS: Snakebites account for one to two NPIS cases per week. Adder bites account for over half of cases. A quarter of cases were due to non-UK snakes kept in captivity within the UK. Envenoming was said to have occurred in just under half of all cases. Advice given by the NPIS appears to closely reflect national practice guidelines.

The efficacy and adverse effects of dicobalt edetate in cyanide poisoning.

INTRODUCTION: Dicobalt edetate is one of a number of cobalt compounds that have been studied in the treatment of cyanide poisoning, their efficacy being based upon the fact that cyanide combines with cobalt to form relatively non-toxic complexes. Inorganic cobalt salts are quite toxic (cyanide and cobalt antagonise one another's toxicity) and complexes such as dicobalt edetate were studied with the aim of identifying compounds that were less acutely toxic, but which retained the antidotal properties of cobalt salts. The proprietary preparation, Kelocyanor™, contains free cobalt and glucose as well as dicobalt edetate. OBJECTIVE: The aim of this study was to evaluate the published evidence for the efficacy and adverse effects of dicobalt edetate. METHODS: A Pubmed search was undertaken for the period 1961-September 2015. The search terms were "dicobalt edetate", "cobalt edetate" and "Kelocyanor", which produced 24 relevant citations. A review of the references in four relevant books (L'intoxication cyanhydrique et son traitement, Clinical and Experimental Toxicology of Cyanides, Antidotes for Poisoning by Cyanide and Antidotes) produced three further relevant papers, making a total of 27 papers. Efficacy of dicobalt edetate: There is evidence from animal pharmacodynamic studies that dicobalt edetate is an effective cyanide antidote in experimental animals. Some 39 cases of human poisoning treated with dicobalt edetate have been reported, but in only nine cases were blood cyanide concentrations measured, although administration of dicobalt edetate procured survival in four of the seven patients with concentrations in the lethal range (>3.0 mg/L). It is unlikely that death in any of the adequately documented fatal cases was attributable to treatment failure with dicobalt edetate, as it is probable that they all had suffered anoxic brain damage before treatment could be initiated. Furthermore, in one case, acute gold toxicity contributed substantially to death. Adverse effects of dicobalt edetate: Adverse effects reported have included hypertension, tachycardia, nausea, retrosternal pain, sweating, palpebral, facial and laryngeal oedema, vomiting, urticaria and/or a feeling of impending doom. Such effects appear to be more prevalent where the antidote has been administered without evidence of substantial systemic poisoning or where other antidotes have been used which might have been expected also to combine with cyanide. Although the adverse effects observed were doubtless unpleasant, and some were severe, no fatal reactions were found. CONCLUSIONS: Dicobalt edetate is an effective cyanide antidote when given to patients with systemic cyanide poisoning, but it has the potential to give rise to adverse reactions, particularly when administered in the absence of intoxication.

Reported toxicity in 1486 liquid detergent capsule exposures to the UK National Poisons Information Service 2009-2012, including their ophthalmic and CNS effects.

CONTEXT. Data on the ophthalmic and central nervous system (CNS) adverse effects of liquid detergent capsules (liquid laundry pods) are limited. OBJECTIVE. To ascertain the reported toxicity of liquid detergent capsules, particularly their ophthalmic and CNS adverse effects, in a large case series. METHODS. Between 1 May 2009 and 30 July 2012 the UK National Poisons Information Service collected prospectively 1509 telephone enquiries (involving 1486 exposures) relating to liquid detergent capsules. RESULTS. The majority of patients (95.6%) were children aged less than 5. Exposure to these products occurred mainly as a result of ingestion alone (n = 1215; 81.8%), with eye contact alone (n = 110; 7.4%), and skin contact alone (n = 20; 1.3%) being less common; multiple routes of exposure were involved in 141 (9.5%) cases. Following ocular exposure (n = 212), features suggesting conjunctivitis (n = 145; 68.4%) and corneal ulceration (n = 6; 2.8%) developed. The most common features reported following ingestion alone were nausea and vomiting (n = 721; 59.3%), followed by coughing (n = 53; 4.4%), drowsiness/CNS depression (n = 49; 42 of these were children were aged 2 years or less) and foaming at the mouth (n = 47; 3.9%). A rash occurred in 22 patients where ingestion was considered to be the route of exposure. Twenty patients were exposed via the dermal route alone and developed erythema (n = 9), rash (n = 6) and burn (n = 3). CONCLUSIONS. Ocular exposure to liquid detergent capsules may lead to conjunctivitis and corneal ulceration; detergent ingestion may result in central nervous system (CNS)depression. Greater consumer awareness is required to reduce injury from liquid detergent capsules, particularly that involving the eye.

Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood mononucleocyte cell histamine release induced by N-acetylcysteine.

INTRODUCTION: The treatment of acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to the antidote. The mechanism that underlies this reaction is unclear. We used the human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs) to investigate the effects of NAC and paracetamol on histamine secretion in vitro. METHOD: HMC-1 and human PBMCs were incubated in the presence of increasing concentrations of NAC +/- paracetamol. Cell viability was determined by the Trypan Blue Assay, and histamine secretion was measured by ELISA. RESULTS: NAC was toxic to HMC-1 cells at 100 mg/mL and to PBMCs at 67 mg/mL. NAC increased HMC-1 and PBMC histamine secretion at concentrations of NAC from 20 to 50 mg/mL and 2.5 to 100 mg/mL, respectively. NAC-induced histamine secretion by both cell types was reduced by co-incubation with 2.5 mg/mL of paracetamol. CONCLUSION: Paracetamol (acetaminophen) is capable of modifying histamine secretion in vitro. This may explain the clinical observation of a lower incidence of adverse reactions to NAC in vivo when higher concentrations of paracetamol are present than when paracetamol concentrations are low. Paracetamol (acetaminophen) attenuates in vitro mast cell and PBMC cell histamine release induced by NAC.