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.

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.