Lead poisoning among asymptomatic individuals with a long-term history of opiate use in Golestan Cohort Study.

BACKGROUND: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use. RESULTS: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use. CONCLUSION: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.

Gadolinium-based contrast agents - what is the evidence for 'gadolinium deposition disease' and the use of chelation therapy?

Introduction: Gadolinium-based contrast agents are widely used for magnetic resonance imaging and, until recently, had been generally considered to have an excellent safety profile in patients with normal renal function. Nephrogenic systemic fibrosis is a well-established disease process involving fibrosis of the skin and internal organs seen in some patients with severely impaired renal function following exposure to these agents. Following reports that individuals with normal renal function may experience gadolinium deposition within brain and bone tissue, the term "gadolinium deposition disease" has been proposed and the use of chelating agents has been recommended to treat this "disease".Objectives: This review will address the clinical evidence for "gadolinium deposition disease" and discuss whether chelation therapy is appropriate for individuals who believe they have this condition.Methods: Electronic databases (PUBMED, Ovid MEDLINE and EMBASE) were searched up to 1st October 2019 for all studies evaluating clinical signs or symptoms related to potential gadolinium toxicity post-gadolinium-based contrast agent exposure in subjects with normal renal function, or papers evaluating the potential chelation of gadolinium in humans.Does "gadolinium deposition disease" exist as a novel condition? We identified four clinical studies relating to "gadolinium deposition disease", including one that included some discussion of the use of chelation therapy. Two of the clinical studies presented data from anonymous online surveys that recruited participants from support forums for people who self-identified as having gadolinium-based contrast agent-induced toxicity, with questions focussing on their reported symptoms and signs. The published literature to date has demonstrated that gadolinium deposition within the brain primarily occurs within the dentate nucleus and globus pallidus. These patients did not complain of movement disorders, but instead reported generalised sensory symptoms, which would not be expected to occur with pathology in these areas of the brain. There was considerable selection bias and a lack of available clinical information to exclude alternative medical diagnoses for these series, thus rendering the results difficult to interpret.Role of chelation therapy in patients exposed to gadolinium-based contrast agent: One study reported data from 25 patients who were diagnosed with "gadolinium deposition disease" according to unspecified criteria and were treated with intravenous calcium or zinc trisodium pentetate. The authors reported an increase in urine gadolinium concentrations following administration of the chelating agents, which they attributed to re-chelation of gadolinium from tissue deposits, however, there are insufficient data to be able to substantiate this.Conclusion: There is currently no published information from well-designed clinical studies that support a link between gadolinium deposition and the development of clinical sequelae in patients with normal renal function. Clinicians should exercise caution when considering whether or not gadolinium is of relevance in patients reporting symptoms after administration of gadolinium-based contrast agents. The inappropriate use of chelation therapy in patients with no clear evidence-based indication for their use potentially increases the risk of clinically significant harm to these patients from the adverse effects of chelation. Further research and well-designed clinical and epidemiological surveillance is needed to determine whether there are toxicological risks related to gadolinium exposure from the use of gadolinium-based contrast agents in patients with normal renal function.

Lesson of the month 1: Acute flecainide overdose and the potential utility of lipid emulsion therapy.

Lipid-emulsion therapy (Intralipid®) has been advocated as a potential treatment for the management of cardio-toxicity arising from lipid-soluble drugs, particularly those acting upon sodium channels. This, on the basis of a number of ex vivo studies and animal models, suggests that partitioning a drug into lipid could alter its pharmacokinetics and result in significant clinical improvements. Its subsequent use in clinical case series has been seen as confirmation of this mechanism of action. While there are undoubtedly instances where lipid emulsion therapy has been associated with a desirable outcome in humans, as described in this case report, clinicians are reminded that they should not attribute causality, on this basis alone.

Outbreak of fatal childhood lead poisoning related to artisanal gold mining in northwestern Nigeria, 2010.

BACKGROUND: In May 2010, a team of national and international organizations was assembled to investigate children's deaths due to lead poisoning in villages in northwestern Nigeria. OBJECTIVES: Our goal was to determine the cause of the childhood lead poisoning outbreak, investigate risk factors for child mortality, and identify children < 5 years of age in need of emergency chelation therapy for lead poisoning. METHODS: We administered a cross-sectional, door-to-door questionnaire in two affected villages, collected blood from children 2-59 months of age, and obtained soil samples from family compounds. Descriptive and bivariate analyses were performed with survey, blood lead, and environmental data. Multivariate logistic regression techniques were used to determine risk factors for childhood mortality. RESULTS: We surveyed 119 family compounds. Of 463 children < 5 years of age, 118 (25%) had died in the previous year. We tested 59% (204/345) of children < 5 years of age, and all were lead poisoned (≥ 10 µg/dL); 97% (198/204) of children had blood lead levels (BLLs) ≥ 45 µg/dL, the threshold for initiating chelation therapy. Gold ore was processed inside two-thirds of the family compounds surveyed. In multivariate modeling, significant risk factors for death in the previous year from suspected lead poisoning included the age of the child, the mother's work at ore-processing activities, community well as primary water source, and the soil lead concentration in the compound. CONCLUSION: The high levels of environmental contamination, percentage of children < 5 years of age with elevated BLLs (97%, > 45 µg/dL), and incidence of convulsions among children before death (82%) suggest that most of the recent childhood deaths in the two surveyed villages were caused by acute lead poisoning from gold ore-processing activities. Control measures included environmental remediation, chelation therapy, public health education, and control of mining activities.

Use of high-resolution accurate mass spectrometry to detect reported and previously unreported cannabinomimetics in "herbal high" products.

A range of "Herbal High" products were tested for synthetic cannabinoids (cannabinomimetics) to qualitatively determine and compare their individual and relative content. Liquid chromatography-high resolution accurate mass spectrometry was used to rapidly screen samples for a range of cannabinomimetics using mono-isotopic masses derived from the elemental composition of target analytes. A screening database of over 140 compounds was rapidly created. This approach, combined with further tandem mass spectrometric experiments, also facilitated the detection and identification of compounds for which reference materials were not available. Previously reported cannabinomimetics, including JWH-018 and CP47,497 and its homologues, were detected in varying relative proportions along with several tentatively identified unreported cannabinomimetics. In some countries, the decision has been made to include these substances within their drug control legislation, and other countries are considering similar action. The currently applied drug screening techniques are unlikely to be effective in providing scientific evidence to support their identification in seized products. The application of high-resolution accurate mass spectrometry offers a solution. In addition, the technology provides a relatively simple and quick method for screening products, building substance databases, and even identifying novel substances using a combination of accurate mass derived elemental composition and fragment ions combined with fragmentation prediction software.

Availability of and use of Intralipid (lipid rescue therapy, lipid emulsion) in England and Wales.

There is increasing evidence for the use of Intralipid in the management of acute local anaesthetic toxicity. This is supported by the recent Association of Anaesthetists of Great Britain and Ireland (AAGBI) guidelines for the management of local anaesthetic toxicity. Acute hospitals in England and Wales were surveyed to determine the proportion that currently stocked Intralipid, the locations of stocks within the hospital, guidelines related to its use and previous use in the last 12 months. The majority of hospitals surveyed stocked Intralipid in multiple locations, although not in all areas using high volumes of local anaesthetics. Guidelines were typically in place, although these were often local rather than those from the AAGBI. Use in the last 12 months was uncommon, but typically information was not available on indications for its use. More systematic data collection is required on the safety and efficacy of Intralipid in the management of acute drug toxicity.

Severe iatrogenic bismuth poisoning with bismuth iodoform paraffin paste treated with DMPS chelation.

BACKGROUND: Bismuth iodoform paraffin paste (BIPP) is used for the packing of wound and surgical cavities. Features of both bismuth and iodoform toxicities have been associated with the use of BIPP, but there are no previous reports of 2,3-dimercaptopropane-1-sulphonate (DMPS) chelation therapy for bismuth poisoning secondary to its use. CASE REPORT: A 67-year-old man presented with a pelvic tumor requiring extensive surgical resection. BIPP packing was required post-operatively for surgical wound breakdown. A few days after insertion, the patient developed neurological features of bismuth toxicity (blood and urine bismuth concentrations were 340 microg/L and 2800 microg/L, respectively), which was treated with removal of the BIPP packing and DMPS chelation [27 days of intravenous DMPS (5 mg/kg 4 times daily for 5 days, 5 mg/kg three times daily for 5 days followed by 5 mg/kg twice a day for 17 days) followed by 24 days of oral DMPS (200 mg three times a day for 10 days, followed 200 mg twice daily for 14 days)]. This resulted in improvement in his symptoms and a decline in his pre-chelation bismuth concentration of 480 microg/L to 5 microg/L following chelation. There were no adverse effects during chelation. CONCLUSIONS: DMPS chelation appears to be a potentially effective chelating agent in bismuth toxicity.

Case report: severe mercuric sulphate poisoning treated with 2,3-dimercaptopropane-1-sulphonate and haemodiafiltration.

INTRODUCTION: Inorganic mercury poisoning is uncommon, but when it occurs it can result in severe, life-threatening features and acute renal failure. Previous reports on the use of extracorporeal procedures such as haemodialysis and haemoperfusion have shown no significant removal of mercury. We report here the successful use of the chelating agent 2,3-dimercaptopropane-1-sulphonate (DMPS), together with continuous veno-venous haemodiafiltration (CVVHDF), in a patient with severe inorganic mercury poisoning. CASE REPORT: A 40-year-old man presented with haematemesis after ingestion of 1 g mercuric sulphate and rapidly deteriorated in the emergency department, requiring intubation and ventilation. His initial blood mercury was 15 580 microg/l. At 4.5 hours after ingestion he was started on DMPS. He rapidly developed acute renal failure and so he was started on CVVHDF for renal support and in an attempt to improve mercury clearance; CVVHDF was continued for 14 days. METHODS: Regular ultradialysate and pre- and post-filtrate blood samples were taken and in addition all ultradialysate generated was collected to determine its mercury content. RESULTS: The total amount of mercury in the ultrafiltrate was 127 mg (12.7% of the ingested dose). The sieving coefficient ranged from 0.13 at 30-hours to 0.02 at 210-hours after ingestion. He developed no neurological features and was discharged from hospital on day 50. Five months after discharge from hospital he remained asymptomatic, with normal creatinine clearance. DISCUSSION: We describe a patient with severe inorganic mercury poisoning in whom full recovery occurred with the early use of the chelating agent DMPS and CVVHDF. There was removal of a significant amount of mercury by CVVHDF. CONCLUSION: We feel that CVVHDF should be considered in patients with inorganic mercury poisoning, particularly those who develop acute renal failure, together with meticulous supportive care and adequate doses of chelation therapy with DMPS.