Mercury Toxicity and Chelation: A Rope of Sand

• Mercury is a naturally occurring heavy metal
  
• Found in elemental, inorganic, and organic forms
• Reacts with sulfhydryl groups in the body to inhibit enzymatic action, rapidly distributes to many organ systems

  Elemental Mercury – used for home metallurgy, gold smithing, thermometers

• Highly volatile at room temperature
  
• 75-80% absorbed via inhalation
  
• Inhalation-> CNS and Kidney Accumulation -> Significant pulmonary effects, but survivable!
  

Guiterrez, F.  Leon, L.  Elemental Mercury Embolism to the Lung.  N Engle J Med 2000; 342: 1791. June 15, 2000.  

Inorganic Mercury

• Usually via intentional ingestion, found in chemistry labs
• Acute exposure can cause hemorrhagic gastroenteritis, shock, ATN
• Chronic exposure responsible for mad hatter syndrome – abdominal pain, tremors, erethism, neurasthenia
• Oral Exposure-> Renal distribution ->GI and Renal symptoms
  
  

Organic Mercury

• Used in some antiseptics, chemical companies to make phenols
• Fat soluble, rapidly bioaccumulates in fish and higher predators
• Neurologic symptoms: ataxia, tremor, visual symptoms, dysarthria
• Oral Exposure -->CNS/Renal/Liver distribution -> Primary Neurologic symptoms
  
  

Lab Evaluation:

• Whole blood level of limited use, poor clinical coorelation
• Hair/Toenail levels also possible, poor correlation in acute exposure
• CBC for anemia, BMP for renal function

Management

• Skin decontamination :  carefully, mercury can vaporize and should not be vaccumed, more than 2 teaspoons requires a specialized team to remove from the hospital setting
• Mercury Decon Kit : Calcium polysulfide to convert to cinnabar
• Elemental Mercury may require intubation and pulmonary support
• Inorganic mercury will require copious IVF for severe third spacing and GI losses.  Can consider charcoal but may be dangerous
• Organic Mercury: Aggressive decontamination

Antidotes – Chelation Therapy!

• All bind to target to increase urinary elimination
• Early chelation provides better outcomes given symptoms and history consistent with mercury exposure

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Dimercaprol (BAL) – Acute elemental and inorganic mercury

• 5 mg/kg/dose q4h IM x 48 hours
• 2.5 mg/kg q6 hr x 48 hours
• 2.5 mg/kg q12 hr x 7
• Also useful in lead, arsenic

Succimer (DMSA): oral alternative for stable patients or those with chronic toxicity from elemental and inorganic mercury

• 10 mg/kg PO TID x 5 days
• 10 mg/kg PO BID x 14 days
  
  

Organic mercury currently is treated in the US with Succimer (DMSA), however in Europe there is an IV/Oral dithiol analog of BAL called DMPS

• Available OTC in Europe, greater water solubility and available in oral forms
• 250 mg IV q4hrs for first 48 hours
• 250 mg IV q6hrs for the next 48 hours
• 250 mg IV q8hrs for the next 48 hours
• 300 mg PO TID for 7 weeks

References
1. Aaseth J, Skaug MA, Cao Y, Andersen O. Chelation in metal intoxication-Principles and paradigms. J Trace Elem Med Biol. 2014
2. Cao Y, Skaug MA, Andersen O, Aaseth J. Chelation therapy in intoxications with mercury, lead and copper. J Trace Elem Med Biol. 2014;
3. George GN, Prince RC, Gailer J, et al. Mercury binding to the chelation therapy agents DMSA and DMPS and the rational design of custom chelators for mercury. Chem Res Toxicol. 2004;17(8):999-1006.
4. Sue Y.  Chapter 96.  Mercury.  In: Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE.  Eds.  Goldfrank’s Toxicologic Emergencies, 9e.  New York, NY: McGraw-Hill 2011. 
5. Guiterrez, F.  Leon, L.  Elemental Mercury Embolism to the Lung.  N Engl J Med 2000; 342: 1791. June 15, 2000.
6. Aaseth J, Jacobsen D, Andersen O, Wickstrøm E. Treatment of mercury and lead poisonings with dimercaptosuccinic acid and sodium dimercaptopropanesulfonate. A review. Analyst. 1995;120(3):853-4.
7. Aposhian HV, Maiorino RM, Gonzalez-ramirez D, et al. Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology. 1995;97(1-3):23-38.
8. Aposhian HV, Bruce DC, Alter W, Dart RC, Hurlbut KM, Aposhian MM. Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. FASEB J. 1992;6(7):2472-6.
9. Aaseth J, Skaug MA, Cao Y, Andersen O. Chelation in metal intoxication-Principles and paradigms. J Trace Elem Med Biol. 2014;
10. Cao Y, Skaug MA, Andersen O, Aaseth J. Chelation therapy in intoxications with mercury, lead and copper. J Trace Elem Med Biol. 2014;
11. Nielsen JB, Andersen O.  Effect of four thiol-containing chelators on disposition of orally administered mercuric chloride.  Hum Exp Toxicol.  1991; 10: 423-430.
12. Planas-bohne F. The effect of 2,3-dimercaptorpropane-1-sulfonate and dimercaptosuccinic acid on the distribution and excretion of mercuric chloride in rats. Toxicology. 1981;19(3):275-8.
13. Clarkson TW, Magos L, Cox C, et al. Tests of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraq outbreak. J Pharmacol Exp Ther. 1981;218(1):74-83.
14. Ruha AM. Recommendations for provoked challenge urine testing. J Med Toxicol. 2013;9(4):318-25.
15. Bates N. Metallic and inorganic mercury poisoning. Emerg Nurse. 2003;11(1):25-31.
16. Guha mazumder DN, De BK, Santra A, et al. Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water. J Toxicol Clin Toxicol. 2001;39(7):665-74.
17. Muran PJ. Mercury elimination with oral DMPS, DMSA, vitamin C, and glutathione: an observational clinical review. Altern Ther Health Med. 2006;12(3):70-5.
18. .Rooney JP. The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury. Toxicology. 2007;234(3):145-56.