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Dear Editor, We read with great interest the letter from Pelclova and Lach [[1]] on the efficacy of unithiol (2,3-dimercaptopropanesulfonate) and acetylcysteine in a patient with arthroplastic cobalt toxicity. Acetylcysteine increases cobalt urinary excretion and consistently maintains the serum cobalt concentration less than the threshold of 10 g/L, which we believe to be the goal in patients with metal-on-metal implants in order to minimise cobalt toxicity from the existing prosthesis [[3]]. The authors stated that chelation therapy, either with unithiol or acetylcysteine, is often clinically inefficient in patients with very elevated cobalt concentrations (greater than 100 g/L) as long as the damaged prosthesis remains I in situ i . [Extracted from the article]

We conclude that treatment with either unithiol or acetylcysteine is inefficient in patients with very elevated serum cobalt concentrations, especially greater than 100 µg/L, as long as the damaged prosthesis remains I in situ i . Dear Editor, Previously [[1]] we reported a 56-year-old man with severe cobalt poisoning from a damaged metal-on-ceramic hip prosthesis. However, her serum cobalt concentration reached 221 µg/L in February 2022 on the day of the surgery, which subsequently decreased to 51 µg/L 11 days after surgery, 10 µg/L 2.5 months after surgery, and 3 µg/L 6 months after surgery, all without further treatment. [Extracted from the article]

Context:Post-arthroplasty metallosis, which refers to metallic corrosion and deposition of metallic debris in the periprosthetic soft tissues of the body, is an uncommon complication. Systemic cobalt toxicity post-arthroplasty is extremely rare. The few known fatal cases of cobalt toxicity appear to be a result of replacing shattered ceramic heads with metal-on-metal or metal-on-polyethylene implants. Friction between residual shards of ceramic and cobalt–chromium implants allows release of cobalt into the synovial fluid and bloodstream, resulting in elevated whole blood cobalt levels and potential toxicity. Case details:This is a single patient chart review of a 60-year-old woman with prior ceramic-on-ceramic right total hip arthroplasty complicated by fractured ceramic components and metallosis of the joint. She underwent synovectomy and revision to a metal-on-polyethylene articulation. Ten months post-revision, she presented to the emergency department (ED) with right hip pain, dyspnea, worsening hearing loss, metallic dysgeusia, and weight loss. Chest CTA revealed bilateral pulmonary emboli (PE), and echocardiogram revealed new cardiomyopathy with global left ventricular hypokinesis with an ejection fraction (EF) of 35–40% inconsistent with heart strain from PE. Whole blood cobalt level obtained two days into her admission was 424.3 mcg/L and 24-h urine cobalt level was 4830.5 mcg/L. Although the patient initially clinically improved with regard to her PE and was discharged to home on hospital day 5, she returned 10 days later with a right hip dislocation and underwent closed reduction of the hip. The patient subsequently decompensated, developing cardiogenic shock, and respiratory failure. She went into pulseless electrical activity (PEA) and expired. Autopsy revealed an extensive metallic effusion surrounding the right hip prosthesis that tested positive for cobalt (41,000 mcg/L). There was also cobalt in the heart muscle tissue (2.5 mcg/g). A whole blood cobalt level obtained two days before she expired was 641.6 mcg/L. Discussion:This is a case of fatal cobalt-induced cardiomyopathy in a patient whose ceramic components of a total hip arthroplasty fractured causing metallosis with worsening cobalt toxicity. We recommend that when a fractured device is revised with a prosthesis with cobalt–chromium components, whole blood and urine cobalt measurements should be obtained and periodically monitored to evaluate for rising concentrations. Providers should be aware of clinical signs and symptoms of cobalt toxicity in patients who have prostheses with cobalt–chromium components. If suspected, toxicology and orthopedics should be involved for possible chelation and removal of the prosthesis. [ABSTRACT FROM PUBLISHER]

Introduction. One in eight of all total hip replacements requires revision within 10 years, 60% because of wear-related complications. The bearing surfaces may be made of cobalt/chromium, stainless steel, ceramic, or polyethylene. Friction between bearing surfaces and corrosion of non-moving parts can result in increased local and systemic metal concentrations. Objectives. To identify and systematically review published reports of systemic toxicity attributed to metal released from hip implants and to propose criteria for the assessment of these patients. Methods. Medline (from 1950) and Embase (from 1980) were searched to 28 February 2014 using the search terms (text/abstract) chrom* or cobalt* and [toxic* or intox* or poison* or adverse effect or complication] and [prosthes* or 'joint replacement' or hip or arthroplast*] and PubMed (all available years) was searched using the search term (('Chromium/adverse effects'[Mesh] OR 'Chromium/poisoning'[Mesh] OR 'Chromium/toxicity'[Mesh]) OR ('Cobalt/adverse effects'[Mesh] OR 'Cobalt/poisoning'[Mesh] OR 'Cobalt/toxicity'[Mesh])) AND ('Arthroplasty, Replacement, Hip'[Mesh] OR 'Hip Prosthesis'[Mesh]). These searches identified 281 unique references, of which 23 contained original case data. Three further reports were identified from the bibliographies of these papers. As some cases were reported repeatedly the 26 papers described only 18 individual cases. Systemic toxicity. Ten of these eighteen patients had undergone revision from a ceramic-containing bearing to one containing a metal component. The other eight had metal-on-metal prostheses. Systemic toxicity was first manifest months and often several years after placement of the metal-containing joint. The reported systemic features fell into three main categories: neuro-ocular toxicity (14 patients), cardiotoxicity (11 patients) and thyroid toxicity (9 patients). Neurotoxicity was manifest as peripheral neuropathy (8 cases), sensorineural hearing loss (7) and cognitive decline (5); ocular toxicity presented as visual impairment (6). All these neurological features, except cognitive decline, have been associated with cobalt poisoning previously. Type of prosthesis and blood metal concentrations. Where blood or serum metal concentrations were reported ( n = 17 for cobalt and n = 14 for chromium), the median cobalt concentration was 398 (range, 13.6-6521) μg/L and the median chromium concentration was 48 μg/L (in whole blood) (range, 4.1-221 μg/L including serum and blood values). Those patients reported to have systemic features who had received a metal-on-metal prosthesis ( n = 8) had a median peak blood cobalt concentration of 34.5 (range, 13.6-398.6) μg/L; those with a metal-containing revision of a failed ceramic prosthesis ( n = 10) had a median blood cobalt concentration of 506 (range, 353-6521) μg/L. Management. The most common treatment was removal of the metal-containing prosthesis, undertaken in all but 2 patients. This was usually associated with a fall in circulating cobalt concentration and improvement in some or all features. Clinical and toxicological assessment of systemic features. We propose the following criteria for assessing the likelihood that clinical features are related to cobalt toxicity: clinical effects consistent with the known neurological, cardiac, or thyroidal effects of cobalt, and for which any other explanation is less likely; increased blood cobalt concentrations (substantially higher than those in patients with well-functioning prostheses) several months after hip replacement; a fall in the blood cobalt concentration, usually accompanied by signs of improvement in features. When judged by these criteria, the systemic features in 10 of the reported cases are likely to be related to cobalt exposure from a metal-containing hip prosthesis. Conclusions. Rarely, patients exposed to high circulating concentrations of cobalt from failed hip replacements develop neurological damage, hypothyroidism and/or cardiomyopathy, which may not resolve completely even after removal of the prosthesis. The greatest risk of systemic cobalt toxicity seems to result from accelerated wear of a cobalt-containing revision of a failed ceramic prosthesis, rather than from primary failure of a metal-on-metal prosthesis. [ABSTRACT FROM AUTHOR]

Introduction. There has been some recent concern regarding possible systemic health effects resulting from elevated blood cobalt concentrations in patients with cobalt containing hip implants. To date there are no blood cobalt criteria to help guide physicians when evaluating an individual hip implant patient's risk of developing systemic health effects because historically there was little or no concern about systemic cobalt toxicity in implant patients. Objective. Our purpose is to describe recently completed research regarding the relationship between blood cobalt concentrations and clinical health effects. We discuss the possibility of systemic health effects in patients with metal containing implants and propose various blood cobalt concentrations that are not associated with an increased risk of developing certain adverse effects. Methodology. The primary literature search was conducted using PubMed and Web of Science using the following search terms: cobalt AND (toxicity OR health effects OR cardiotoxicity OR hematological OR endocrine OR immunological OR reproductive OR testicular effects OR neurological OR case report OR cohort OR Roncovite). The searches identified 6786 papers of which 122 were considered relevant. The Agency for Toxic Substances and Disease Registry toxicological profile for cobalt and the U.S. Environmental Protection Agency Office of Research and Development's National Center for Environmental Assessment's documentation on the provisional peer-reviewed toxicity value for cobalt were also utilized to identify secondary literature sources. Results. Our review of the toxicology and medical literature indicates that highly elevated blood cobalt concentrations can result in certain endocrine, hematological, cardiovascular, and neurological effects in animals and/or humans. These studies, in addition to historical clinical findings involving the therapeutic use of cobalt, indicate that significant systemic effects of cobalt will not occur below blood cobalt concentrations of 300 μg/L in most persons. Some individuals with specific risk factors for increased susceptibility (e.g., severe and sustained hypoalbuminemia) may exhibit systemic effects at lower cobalt blood concentrations. This review also describes several cobalt dosing studies performed with human volunteers that consumed cobalt for 15, 30, or 90 days. Overall, the results of these dosing studies indicate that sustained blood cobalt concentrations averaging 10-70 μg/L for up to 90 days cause no significant clinical effects (maximum concentrations approached 120 μg/L). Some proposed blood criteria for assessing implant wear and local tissue damage have been suggested by several medical groups. For example, the UK Medicines and Healthcare Products Regulatory Agency has proposed a blood cobalt guidance value of 7 μg/L, and the Mayo Clinic has suggested serum cobalt concentrations greater than 10 μg/L, but both of these values are primarily intended to address implant wear and to alert physicians to the possibility of an increased incidence of local effects. There is a clear lack of consensus regarding how to identify a specific numerical blood concentration of concern and whether whole blood or serum is a better matrix to assess total cobalt concentration. Conclusions. Based on currently available data, only under very unusual circumstances should a clinician expect that biologically important systemic adverse effects might occur in implant patients with blood cobalt concentrations less than 300 μg/L. Patients with metal-containing hip implants who exhibit signs or symptoms potentially related to polycythemia, hypothyroidism, neurological, or cardiac dysfunction should be clinically evaluated for these conditions. Polycythemia appears to be the most sensitive endpoint. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the concentration of cobalt (Co) and chromium (Cr) ions in synovial fluid, blood plasma and cerebrospinal fluid (CSF) of patients with metal-on-metal (MoM) implants, and to assess the relationship between implant history and patient characteristics with ion concentrations in CSF. Methods: An observational, non-randomised cross-sectional study was conducted with patients presenting to a single surgeon for treatment of degenerative conditions of the hip and knee. Blood and fluid samples were collected intraoperatively and analysed for proteins and trace elements. Results: Overall, the presence of an implant was associated with significantly higher Co and Cr concentrations in plasma (controls 5–115 nmol/L Co, 5–232 nmol/L Cr; well-functioning implant recipients 5–469 nmol/L Co, 5–608 nmol/L Cr; hip revisions 6–546 nmol/L Co, 5–573 nmol/L Cr), and for Cr concentrations in CSF (controls 5–24 nmol/L; well-functioning implant recipients 6–36 nmol/L, hip revisions 7–32 nmol/L). In absolute terms, <1% of the levels observed in the joint fluid and <15% of plasma metals appeared in the CSF. Multivariable regression models suggested different transfer mechanisms of Co and Cr to the CSF, with the presence of an implant not associated with ion levels. Conclusion: The presence of MoM implants is associated with significantly higher plasma levels of Co and Cr but not CSF levels, and the CSF/plasma ratio appears to be influenced by the plasma concentration in a nonlinear fashion. Co and Cr may be transferred to the CSF by different mechanisms, and their concentrations appears dependent on other factors yet to be identified. Although higher levels of plasma ions are associated with above average CSF metal concentrations, the thresholds for neurotoxicity remain unclear and require further study. [ABSTRACT FROM AUTHOR]

Background: Dilated cardiomyopathy is a frequent disease responsible for 40-50% of cases of heart failure. Idiopathic cardiomyopathy is a primary disorder often related to familial/genetic predisposition. Before the diagnosis of idiopathic cardiomyopathy is made, clinicians must not only rule out viral and immune causes, but also toxic causes such as drugs, environmental agents, illicit substances and natural toxins. Objective: The objective of this review is to present recent data on the mechanisms underlying toxic cardiomyopathy. Methods: The US National Library of Medicine Pubmed database was searched from 1980 to December 2017 utilizing the combinations of the search terms "toxic cardiomyopathy", "drugs", "anticancer drugs", "azidothymidine", "rosiglitazone", "carbon monoxide", "alcohol", "illicit drugs", "cocaine", "metamfetamine", "metals", "venom". A total of 339 articles were screened and papers that dealt with the pathophysiology of toxic cardiomyopathy, either in animal models or in clinical practice were selected, with preference being given to more recently published papers, which left 92 articles. Anticancer drugs: The mechanisms of anthracycline-induced cardiotoxicity are primarily related to their mechanisms of action as anticancer drugs, mainly the inhibition of topoisomerase II β and DNA cleavage. Additional metabolic or oxidative stress factors may play a part, together with interference with iron metabolism. The more recent drugs, trastuzumab and imatinib, also influence stress pathways. Antiretroviral agents: Azidothymidine is cardiotoxic as a result of mitochondrial toxicity. In addition to energy depletion, azidothymidine also increases the production of mitochondrial reactive oxygen species (ROS). Antidiabetic drugs: The cardiotoxicity of thiazolidinedione antidiabetic drugs is still under investigation, though interference with mitochondrial respiration or oxidative stress is suspected. Cocaine: Among the multiple mechanisms involved in cocaine-related cardiotoxicity, excessive sympathetic stimulation with increased myocardial oxygen consumption is well documented in the acute form of left ventricular dysfunction. As for cocaine-related cardiomyopathy, the role of apoptosis and ROS is under investigation. Ethanol: The aetiology of ethanol-related cardiotoxicity is multifactorial, with individual susceptibility being important. It involves apoptosis, alterations of the excitation-contraction coupling in cardiac myocytes, structural and functional alterations of the mitochondria and sarcoplasmic reticulum, changes in cytosolic calcium flows, changes in calcium sensitivity of myofilaments, alterations of mitochondrial oxidation, deregulation of protein synthesis, decrease of contractile proteins and disproportion between the different types of myofibrils, changes in the regulation of myosin ATPase, up-regulation of the L-type calcium channels, increase of oxidative stress, and induction of ANP and p21 mRNA expression in ventricular myocardium. Metamfetamines: Catecholamine-mediated toxicity is the probable cause, with a possible role for genetic susceptibility. Carbon monoxide: In addition to hypoxic injury, carbon monoxide is also directly toxic to the mitochondria, with impairment of mitochondrial respiratory chain at the cytochrome c oxidase level, decrease of glutathione concentrations and of ATP production. There is no evidence for a delayed dilated cardiomyopathy in survivors of an acute exposure. Metals: Cobalt-related cardiomyopathy probably results from interference with energy production and contractile mechanisms, but additional factors (nutrition, hypothyroidism) are often required. Antimony may cause lethal oxidative stress and cell death mediated by elevation in intra-cellular calcium. Proposed mechanisms for mercury toxicity include glutathione depletion, production of ROS, and interruption in selenium-dependent endogenous enzymatic reactions. The existence of a lithium-induced cardiomyopathy is still debated. Scorpion venom: Catecholamine release is the probable cause of acute cardiomyopathy following scorpion envenomation. Conclusions: The mechanisms behind toxic cardiomyopathy are complex and multifactorial but include interference with myocardial cell bioenergetics and intracellular calcium handling, the generation of ROS, neurohormonal stress, and induction of apoptosis. [ABSTRACT FROM AUTHOR]

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 CyanideandAntidotes) 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. [ABSTRACT FROM AUTHOR]

Abstracts for the 36th International Congress of the European Association of Poisons Centres and Clinical Toxicologists on May 24-27, 2016 in Madrid, Spain are presented including "Liquid Detergent Capsules: How to Make the Product and Its Use Safer" by Jan Meulenbelt et al, "Hot-cold Packs: Trifle or Threat?" by Jutta Trompelt et al and "An Analytically-Confirmed Case of Benzylglycinamide Consumption" by Antonella Valli, Pietro Papa and Carlo A. Locatelli.

Background:This is the 32nd Annual Report of the American Association of Poison Control Centers’ (AAPCC) National Poison Data System (NPDS). As of 1 January 2014, 56 of the nation’s poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 7.82 [7.02, 11.17] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system. Methodology:We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1–6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death. Results:In 2014, 2,890,909 closed encounters were logged by NPDS: 2,165,142 human exposures, 56,265 animal exposures, 663,305 information calls, 6,085 human confirmed nonexposures, and 112 animal confirmed nonexposures. US poison centers (PCs) also made 2,617,346 follow-up calls in 2014. Total encounters showed a 5.5% decline from 2013, while health care facility human exposure cases increased by 3.3% from 2013. All information calls decreased by 17.7% and health care facility (HCF) information calls were essentially flat, decreasing by 0.04%, medication identification requests (Drug ID) decreased 29.8%, and human exposures reported to US PCs decreased 1.1%. Human exposures with less serious outcomes have decreased 3.40% per year since 2008 while those with more serious outcomes (moderate, major or death) have increased by 4.29% per year since 2000. The top 5 substance classes most frequently involved in all human exposures were analgesics (11.3%), cosmetics/personal care products (7.7%), household cleaning substances (7.7%), sedatives/hypnotics/antipsychotics (5.9%), and antidepressants (4.4%). Sedative/Hypnotics/Antipsychotics exposures as a class increased the most rapidly (2,368 calls (12.2%)/year) over the last 13 years for cases showing more serious outcomes. The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (14.0%), household cleaning substances (11.0%), analgesics (9.3%), foreign bodies/toys/miscellaneous (6.7%), and topical preparations (5.8%). Drug identification requests comprised 43.3% of all information calls. NPDS documented 1,835 human exposures resulting in death with 1,408 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). Conclusions:These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures, despite a decrease in calls involving less serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, viral, bacterial, venomous, chemical agent, or commercial product), the identification of events of public health significance, resilience, response and situational awareness tracking. NPDS is a model system for the real-time surveillance of national and global public health.NOTE: Comparison of exposure or outcome data from previous AAPCC Annual Reports is problematic. In particular, the identification of fatalities (attribution of a death to the exposure) differed from pre-2006 Annual Reports (see Fatality Case Review – Methods). Poison center death cases are described as all cases resulting in death and those determined to be exposure-related fatalities. Likewise, Table 22 (Exposure Cases by Generic Category) since year 2006 restricts the breakdown of included deaths to single-substance cases to improve precision and avoid misinterpretation. [ABSTRACT FROM PUBLISHER]

The article presents abstracts on medical topics which include an online poison information web resource, Russell's viper envenomation, and alcohol-related emergency department visits.

The article presents abstracts on clinical toxicology which include the production of mitochondrial dysfunction from diglycolic acid (DGA), link between the antiemetic ondansetron and cardiac events in adult and elderly hospitalized patients, and the use of high dose ketamine for excited delirium syndrome (ExDS).

The article presents abstracts on clinical toxicology topics for the XXXIV International Congress of the European Association of Poisons Centers and Clinical Toxicologists (EAPCCT) to be held on May 27-30, 2014 in Brussels, Belgium and presents author index for the journal "Clinical Toxicology."

The article presents abstracts on clinical toxicology which includes "New insights in marine toxicology" by Luc de Haro, "Fatal salicylate levels can be lower than expected" by Thomas G Martin and "Pregabalin: An assessment of its toxicity" by Dagmar Prasa and colleagues.

Context. With regard to biological effects, the increasing number of early failure of metal-on-metal (MoM) hip arthroplasties and possible parenteral exposure to orthopedic metal alloys have caused concern for patients and providers alike. Objective. We sought to characterize our outpatient clinical experience of patients with MoM and other forms of hip implants and associated serum/blood chromium and cobalt levels, with a focus on possible systemic sequelae. Methods. This was an observational and retrospective chart review of consecutive patients presenting to two outpatient medical toxicology clinics from January 1, 2010-June 1, 2012 with history of hip implants. Presenting signs, symptoms, and interventions were reviewed. Available cobalt and chromium levels were summarized as median concentration with interquartile range. Results. A total of 39 patients were analyzed; of the 39 patients, 26 had MoM hip implants while 13 did not. Twelve patients exhibited no symptoms and nine sought evaluation for fatigue while two other patients had been previously diagnosed with fibromyalgia. Tinnitus/hearing loss was also a frequent complaint noted in 12 patients (one presenting complaint), however there was no difference between the incidence of this symptom between the MoM and non-MoM groups. Three patients were provisionally diagnosed with demyelinating neuropathy with one patient demonstrating marked (subjective and objective) improvement after revision. Patients with MoM arthroplasties generally exhibit an approximately tenfold increase in metal ion levels than traditional arthroplasties. Finally, 20 (51.2%) patients had replacement or revision of their hip implant with subsequent decreases in metal ion levels. Discussion. A majority of our patients had minor symptoms (fatigue and muscle aches) or no symptoms (n = 23 or 59%). Documented peripheral neurotoxicity is uncommon. The decision for hip revision solely for toxicologic reasons is rare and usually involves a multidisciplinary approach. Conclusion. Most patients seeking toxicologic referral may be minimally symptomatic and seek guidance regarding elevated blood or serum metal ions; however, solely toxicologic-based interventions are unusual. Revision was associated with a decrease in metal ion levels; however, subjective complaints did not correlate with metal ion levels. [ABSTRACT FROM AUTHOR]

Introduction. On theoretical grounds, hydroxocobalamin is an attractive antidote for cyanide poisoning as cobalt compounds have the ability to bind and detoxify cyanide. This paper reviews the pharmacokinetic and pharmacodynamic aspects of hydroxocobalamin, its efficacy in human cyanide poisoning and its adverse effects. Methods. PubMed was searched for the period 1952 to April 2012. A total of 71 papers were identified in this way; and none was excluded. Pharmacokinetics and pharmacodynamics. Pharmacokinetic studies in dogs and humans suggest a two-compartment model, with first order elimination kinetics. Pharmacodynamic studies in animals suggest that hydroxocobalamin would be a satisfactory antidote for human cyanide poisoning. Efficacy in human poisoning. There is limited evidence that hydroxocobalamin alone is effective in severe poisoning by cyanide salts. The evidence for the efficacy of hydroxocobalamin in smoke inhalation is complicated by lack of evidence for the importance of cyanide exposure in fires and the effects of other chemicals as well as confounding effects of other therapeutic measures, including hyperbaric oxygen. Evidence that hydroxocobalamin is effective in poisoning due to hydrogen cyanide alone is lacking; extrapolation of efficacy from poisoning by ingested cyanide salts may not be valid. The rate of absorption may be greater with inhaled hydrogen cyanide and the recommended slow intravenous administration of hydroxocobalamin may severely limit its clinical effectiveness in these circumstances. Adverse effects. Both animal and human data suggest that hydroxocobalamin is lacking in clinically significant adverse effects. However, in one human volunteer study, delayed but prolonged rashes were observed in one-sixth of subjects, appearing 7 to 25 days after administration of 5 g or more of hydroxocobalamin. Rare adverse effects have included dyspnoea, facial oedema, and urticaria. Conclusions. Limited data on human poisonings with cyanide salts suggest that hydroxocobalamin is an effective antidote; data from smoke inhalation are less clear-cut. Although clinically important reactions to hydroxocobalamin have not been seen, some, non-life threatening, adverse reactions can occur. [ABSTRACT FROM AUTHOR]

Context. Cobalt intoxication has become more frequent due to the wide use of metal hip implants. Case details. A 56-year-old male patient underwent total hip prosthesis, with a ceramics-on-ceramics implant. Almost 3 years later, it was replaced by metal implant containing cobalt, chromium, and titanium. He developed weight loss, heart, thyroid, and neurological toxicity, with severe hearing loss. He was treated with 2,3-dimercaptopropane-1-sulfonate (DMPS), and cobalt excretion increased. Clinical symptoms apart from deafness gradually resolved. Conclusion. We report significant cobalt poisoning from a damaged hip replacement with cobalt containing implant and a slow abrasion of the metal by residual ceramic particles. Chelation therapy resulted in apparent benefit. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Interpreting cobalt blood concentrations in hip implant patients" by D. J. Paustenbach, D. A. Galbraith and B. L. Finley in previous issue.

A letter to the editor is presented in response to the article "Interpreting cobalt blood concentrations in hip implant patients" by D. J. Paustenbach, D. A. Galbraith and B. L. Finley in previous issue.