Antimony Toxicity | Treatment & Management | Point of Care (2024)

Etiology

Exposure and toxicity typically occur through inhaling dust particles or fumes containing antimony. Electronic waste recycling workers have significant exposure to antimony, as do smelters; antimony is often found in ore containing arsenic, and coexposure is common.[19][20]Antimony is often present in urine samples of refinery workers, chemical manufacturers, and battery manufacturers.[11]

Stibine exposure is prevalent in the process of charging batteries.[3]Stibine is formed from antimony and hydrogen. Antimony can also be found in cigarette smoke; toxicity is more likely in smokers.[21] Maintenance workers are advised to avoid using drain cleaners containing sodium hydroxide, which is capable of releasing hydrogen ions in situations where antimony is present.[18]

Although toxicity is generally associated with occupational exposure, people living near sources of antimony may be exposed via air, soil, and vegetation. The general population may also be exposed secondary to ingestion of food, water, or contaminated soil or dust.[11]Antimony toxicity can be seen with the use of medicinal antimonial compounds infrequently used in high-resource countries; medical professionals may be unfamiliar with dosing and administration guidelines. Acute antimony overdose is rare and typically is secondary to alcohol aversion treatment.[6]

Epidemiology

Antimony toxicity is rare and may be underreported and underdiagnosed. Results from a study conducted by the National Institute for Occupational Safety and Healthbetween 1981 and 1983 estimated that 486,347 workers were exposed to antimony and its various compounds. The frequency, concentration, and duration of exposure were not reported. Reported urinary antimony levels in battery workers were 5 times higher than other workers. In China, the highest levels of hair antimony levels were present in people involved in electronic waste recycling.[11]

Studies comparing antimony toxicity in children to adults are not available. Rat studies have suggested that antimony may be transferred transplacentally and through breast milk. Plasma antimony levels in children following weight-based intramuscular meglumine antimoniate for leishmaniasis were statistically lower compared to adult counterparts, with a statistically significant shorter half-life in children.[11]

Pathophysiology

Antimony toxicity can be subtle, especially in cases of chronic toxicity; the clinical presentation is variable. The most common presenting sign or symptom is localized irritationthat correlates to the concentration of antimony exposure. Ophthalmic exposure to antimony pentoxide can cause caustic injury, corneal burns, optic atrophy, uveitis, and retinal hemorrhage that may be permanent.[22]

Gastrointestinal manifestations of antimony toxicity are also very common; typical symptoms include nausea, vomiting, and abdominal pain.[6][23] Antimony pentachloride reacts with water in saliva to produce hydrochloric acid, heat, and antimony pentoxide. The hydrochloric acid produced in this reaction can lead to gastrointestinal burns; severe overdoses may result in hemorrhagic gastritis. Treatment of pentavalent antimonial compounds such as meglumine antimoniate and sodium stibogluconate may lead to pancreatitis, especially in patients with HIV.[24][25][26]

Antimony compoundsdecrease cardiac contraction and lower vasomotor tone, resulting in lower systolic pressure and bradycardia.[3][27]Pentavalent antimonial compounds, including sodium stibogluconate and meglumine antimoniate, can lead to QT prolongation, torsades de pointes, ST-segment changes, and T-wave abnormalities by increasing cardiac calcium currents and subsequent action potential prolongation.[28][29][30][31]These changes are more likely in patients with underlying cardiac disease.[32] Meglumine antimoniate is associated with an increased risk of pericarditis.[33] Antimony compounds may also be associated with cardiomyopathy.[34]Additionally, data obtained from the National Health and Nutrition Examination Survey (NHANES) has suggested a positive correlation between antimony exposure in combination with other metals and the risk of cardiovascular disease.[35]

Local respiratory tract irritation can lead to pneumonitis, tracheitis, and laryngitis, especially in exposure to antimony trioxide.[20][36]Cases of acute respiratory distress syndrome have been described following acute antimony pentachloride exposure.[37] Chronic exposure is associated with “antimony pneumoconiosis” which may progress to chronic obstructive pulmonary disease.[38] Radiographic manifestations may yieldmultiple small opacities with a predominant distribution in the middle and lower lung fields.[39]

Antimony compounds may cause nephrotoxicity. Sodium stibogluconate exposure can lead to acute kidney injury, renal tubular acidosis with subsequent hyperchloremic metabolic acidosis, and acute tubular injury, especially in older patients and those with chronic kidney disease.[40][41][42][43]Antimony exposure may also lead to drug-induced interstitial nephritis that typically responds to steroids.[44] Severe stibine exposure may result in hematuria, rhabdomyolysis, and death.[45]

Acute liver injury may be a result of acute antimony toxicity.[6] Chronic antimony exposure may lead to hepatotoxicity, especially in older patients.[46] Fulminant liver failure may be seen despite an initial response to therapy. The proposed injurious mechanism combines immunologic hepatic injury and direct antimony effect.[47][48] Ascorbic acid administration has been shown to provide hepatic protection.[49]

Hematologic effects of antimony toxicity may also be seen. Sodium stibogluconate has been shown to cause severe anemia in patients who are HIV-positive, with resolution after drug cessation.[50] Thrombocytopenia has also been seen with the use of sodium stibogluconate but may be secondary to pancytopenia induced by visceral leishmaniasis.[51] Stibine exposure has a strong association with massive hemolysis; this is believed to be due to the fixation of stibine molecules to sulfhydryl groups of hemoglobin, leading to oxidative stress and erythrocyte injury, as seen in arsine toxicity.[52]

Pentavalent antimony compounds can produce neurological manifestations. Sodium stibogluconate may lead to cerebellar ataxia and reversible peripheral neuropathy, while meglumine antimoniate may lead to vestibulocochlear toxicity with symptoms of tinnitus, increased auditory threshold, and rotatory dizziness.[53][54][55]Development of tremors, extrapyramidal symptoms, and generalized tonic-clonic seizures associated with the antimonial treatment of leishmaniasis have also been documented.[56]

Antimony may be carcinogenic, with antimony trioxide labeled as a group 2B carcinogen.[57]Stibine and trimethylstibine are genotoxic, theoretically due to the generation of reactive oxygen species. Other antimony compounds, including potassium antimony tartrate, trimethylantimony dichloride, and potassium hexahydroxyantimonate are not carcinogenic.[17] Trivalent antimony partially impairsnucleotide excision repair, suggesting anindirect mechanism of carcinogenesis.[57] However, evidence of antimony-induced carcinogenesisis inconclusive. Rat studies have shown an increase in pulmonary tumors in those exposed to antimony trioxide and antimony trisulfide.[58]Results from a human study showed an increased incidence of lung cancer in smelters compared to the unexposed population but did not account for other factors, including arsenic concomitant exposure and tobacco smoking.[59]Other data has failed to replicate this increased risk of lung cancer in exposed workers.[39] There also has been an increased incidence of bladder tumors in patients being treated for leishmaniasis with potential attribution to antimonial compounds, with higher serum antimony concentrations being associated with a worse prognosis.[3][60]In addition, it has been proposed that low-dose antimony exposure may promote the proliferation of prostate cancer by inhibiting ferroptosis.[61]

Toxico*kinetics

Antimony may be absorbed through inhalation, oral ingestion, or transdermally. Oral bioavailability is 15% to 50%, and gastrointestinal absorption begins rapidly after ingestion.[62][63]The degree of inhalational absorption depends on the specific compound. Inorganic compounds are absorbed more slowly and have minimal water solubility. Trivalent compounds have higher levels of absorption.[64]

The distribution of antimony is dependent on the oxidation state and route of administration. Trivalent antimony is typically bound to red blood cells, while pentavalent antimony tends to remain in serum.[11] Orally or intravenously administered antimony is largely distributed to organs that are highly vascularized, including the liver, thyroid, adrenals, and kidneys—with pentavalent forms being distributed primarily to the liver and spleen and trivalent forms being distributed mainly to the thyroid.[3][11][46]Inhaled antimony is primarily bound to red blood cells, with lower concentrations in the liver and spleen.[64]

Metabolic conversions of antimony are limited in humans. Pentavalent antimony is converted to its trivalent form in the liver or acidic intracellular environments of cells infected with Leishmania.[3][65]Antimony may be transformed by forming covalent bonds with sulfhydryl or phosphate groups, being incorporated into lipid molecules, or binding to macromolecules.[11]The excretion of antimony also depends on the oxidative state. Trivalent antimony is conjugated with glutathione and excreted in the bile, with most undergoing enterohepatic recirculation and the residual being slowly eliminated by urine.[8]Pentavalent antimony is more quickly excreted in the urine.[3]

History and Physical

When obtaining a medical history from a patient with suspected antimony exposure, documenting the route of exposure is imperative. Duration and concentration of exposure, risk of coexposure or coingestion, and preexisting medical conditions such as renal disease, liver disease, cardiovascular disease, HIV, and tobacco use should be ascertained. In acute ingestions, suicidal and homicidal ideations should be addressed. The review of systems should include ocular irritation or pain, skin rash, nasopharyngeal irritation, epistaxis, anorexia, nausea, vomiting, diarrhea, hematemesis, melena, hematochezia, abdominal pain, respiratory difficulty or distress, cough, chest pain, palpitations, decreased urinary output, tinnitus, and vertigo.

The physical examination findings of a patient with antiony toxicity are variable. Antimony toxicity primarily presents with local irritation. Patients may have skin findings of pustules and papules consistent with “antimony spots” developing around sebaceous and sweat glands.[66] Chronic exposure may result in lichenification and eczema of the extremities and joint spaces, sparing the face, hands, and feet. Such findings typically occur in warmer summer months.[36] In antimony hypersensitivity reactions, patients may have urticarial lesions, eczema, subcutaneous nodules, or symptoms of anaphylaxis, including wheezing and gastrointestinal distress. Rashes consistent with contact dermatitis may also occur.[67] Patients may also have inflammation of the nasal and oropharyngeal cavities. Thrombophlebitis may be present.[23]Ocular findings may be present, including decreased visual acuity and ocular pain and irritation.[22]

Patients may have abdominal tenderness, especially when accompanied by gastrointestinal symptoms, and may have a garlic-like odor on the breath, but this could be secondary to arsenic coexposure. In severe cases, gastrointestinalhemorrhage may be present.[23]Cardiopulmonary auscultation may reveal an irregular rhythm, tachypnea, hypoxia, coarse breath sounds, or wheezing. In the presence of hepatic injury, patients may have jaundice, scleral icterus, ascites, or altered mental status. Hematologic manifestations may present with skin or conjunctival pallor, petechiae, purpura, or mucosal bleeding. Neurologically, patients may have peripheral neuropathy, nystagmus, and rotatory dizziness.[53][55]

Evaluation

When evaluating suspected or known antimony toxicity, laboratory studies should include complete blood count, electrolyte levels, serum glucose, renal function studies, and urinalysis. In acute toxicity, assessment of volume depletion and renal injury should be prioritized. In the case of stibine exposure, bilirubin, serum lactate dehydrogenase, and haptoglobin should be added to evaluate for hemolysis; blood type and cross-matching should be obtained due to the high likelihood of blood transfusion.[52]

An electrocardiogram should be obtained to assess for QT interval prolongation or dysthymias. Continuous cardiac monitoring is recommended.[32] Chest radiography may be useful in patients with hypoxia or other respiratory symptoms.[39] Abdominal imaging may be useful in patients with gastrointestinal symptoms.[68] For caustic injuries, endoscopy may be indicated if the patient has stridor, drooling, or vomiting. Computed tomography imaging may be reasonable in suspected malignancy secondary to exposure. Most serum antimony levels are not typically processed in-house at most hospitals and thus are not helpful on initial evaluation. Normal antimony concentration in unexposed patients is less than 3 mcg/L.[69] Urine antimony levels in a 24-hour collection may also be obtained, with normal levels less than 6.2 mcg/L.[70]

Treatment / Management

When antimony exposure is suspected or confirmed, consulting with a medical toxicologist or poison control for expert recommendations is recommended. The mainstay of treatment is supportive care. The patient’s respiratory and mental status should be assessed. Endotracheal intubation should be performed if there is airway compromise. Massive volume depletion should be anticipated, with replacement utilizing isotonic crystalloid solutions. Blood products may be indicated in cases of hemolysis secondary to stibine exposure. Renal status, urinary output, electrolyte levels, and hepatic function should be closely monitored.[6] Antiemetics may be used for symptomatic control. Official management guidelines have not been formally established, given the low incidence of antimony toxicity.(B3)

Decontamination in the setting of acute toxicity should be considered and performed in a timely manner. Dermal exposures to antimony compounds should be irrigated with soap and water. In acute ingestion, gastric lavage is reasonable to perform. Activated charcoal may theoretically absorb antimony compounds, and multiple doses may be required given the high degree of enterohepatic circulation of antimony if the patient can tolerate administration.[71] Whole bowel irrigation is recommended in severe ingestion based on the patient's tolerance.The irrigation should be performed within 48 hours based on reports of arsenic poisoning and antimony’s similar chemical properties and toxicologic manifestations.[72] If gastrointestinal burns secondary to antimony pentachloride exposure are suspected, esophagogastroduodenoscopy performed by gastroenterology is indicated. Hemodialysis is indicated in the oliguric phase of acute toxicity with renal injury.[6](B3)

Stibine exposure should be managed with prompt removal from the exposure area while employing appropriate safety precautions for rescuers. Administration of high-flow supplemental oxygen should occur after removal. In theory, exchange transfusion may be beneficial for removing the hemoglobin-stibine complex but cannot be routinely recommended due to insufficient data.[45]

Animal experimentation demonstrated improved survival in the chelation of antimony with dimercaprol, succimer, and dimercaptopropane-sulfonic acid (DMPS), with the most effective treatments being succimer and DMPS.[73][74] However, human data is limited given the rarity of antimony toxicity, with a small subset receiving chelation treatment. Some small human study results have shown increased survival after the administration of dimercaprol.[71] Administering intramuscular dimercaprol may be practical until antimony is removed from the gastrointestinal tract, after which transitioning to oral succimer is advisable. Chelation should be ceased if respiratory symptoms with electrocardiogram changes occur.[6] Chelation dosage in the antimony toxicity setting has not been established. The administration of effective dosages for arsenic and other similar metals is reasonable.(B3)

Managing antimony toxicity requires an interdisciplinary approach involving primary care or emergency medicine clinicians alongside a medical toxicologist.Occupational health specialists may be involved if toxicity is due to occupational exposure. Depending on the affected organ systems, consultants may include ophthalmologists, gastroenterologists, nephrologists, hematologists, pulmonologists, cardiologists, dermatologists, oncologists, endocrinologists, and neurologists.

Differential Diagnosis

In the acute setting, concomitant ingestion and accompanying exposure to other toxic agents must be considered. Antimony toxicity may mimic presentations of other heavy metal poisoning such as arsenic, aluminum, barium, bismuth, cadmium, chromium, cobalt, copper, gold, iron, lead, lithium, manganese, mercury, nickel, phosphorus, selenium, silver, thallium, tin, and zinc. Accompanying exposure to other heavy metals may also be present. Careful history-taking and knowledge of routes of exposure may help differentiate. Serum, urine, and hair levels of other heavy metals may also be obtainable.

Prognosis

The prognosis of antimony toxicity is mostly dependent on the degree of exposure and clinical manifestations. There has been an observed increase in lung cancer-related deaths in workers exposed to antimony compounds.[11] Mortality may also be seen in patients with massive hemolysis, acute renal failure, acute respiratory failure, and acute hepatic failure.

Complications

There are many complications of antimony toxicity given its effect on multiple organ systems. Perhaps the most deadly include life-threatening arrythmia, massive hemolysis, acute respiratory failure, acute renal failure, and acute hepatic failure. Patients have also expired due to sepsis secondary to pancreatitis. Antimony may also lead to permanent ophthalmic, pulmonary, and neurological changes. In addition, patients may have sequelae of malignancies associated with antimony exposure.

Deterrence and Patient Education

Multiple organizations have set antimony exposure limits for workplace environments. The Occupational Health and Safety Administration has set a legal airborne possible exposure limit of 0.5 mg/m³ averaged over an 8-hour shift, while the National Institute for Occupational Safety and Health has a recommended exposure limit of 0.5 mg/m³ for antimony and 0.1 mg/m³ for stibine averaged over a 10-hour shift.[11]Workplace controls such as labeling containers, providing education on potential hazards, monitoring airborne antimony concentrations, providing emergency showers and eye wash fountains, requiring employees to shower at the end of their shift and avoid taking clothing that may be contaminated home, and good hand washing practices are recommended. Employees should be encouraged to use personal protective equipment, including gloves and clothing that cannot be permeated by antimony compounds, direct vent goggles, and respirators when potential exposure over 0.5 mg/m³ is present.[75]In situations of exposure, patients should be removed from the area of exposure, remove contaminated clothing, remove contact lenses, and flush their eyes. Bystanders should be prepared to start artificial respiration and cardiopulmonary resuscitation if necessary. Prompt transfer to a medical facility should be arranged.

Enhancing Healthcare Team Outcomes

The approach and prevention of antimony toxicity should be taken in a collaborative effort among various healthcare professionals. Primary care and occupational and preventative medicine clinicians should educate patients who are at risk of antimony exposure about the proper use of personal protective equipment and preventative measures. Primary care clinicians should also be aware of the symptoms and signs concerning chronic antimony toxicity. Providers administering antimonial compounds for medicinal purposes must be cognizant of the potential adverse events of such treatments. Emergency medicine healthcare professionals should be aware of manifestations of acute toxicity.

Specialists such as ophthalmologists, gastroenterologists, nephrologists, hematologists, pulmonologists, cardiologists, dermatologists, oncologists, endocrinologists, and neurologists may also be involved depending on affected organ systems. Medical toxicologists and poison control centers should be consulted for expert advice. Communication and knowledge sharing between individuals should be clear and respectful. By ensuring high-quality communication and corroborative effort among various members of the healthcare team, patients will have higher-quality care and more favorable outcomes.