Heavy Metal Detoxification
Removal of Exposure Source
The first step in mitigating the toxic effects of acute or chronic metal exposure is removal of the source of contamination. For acute exposures, this may involve (depending on the route of exposure) decontaminating the area of exposure, removing contaminated clothing, and/or removing the individual from the area where exposure occurred (Flora 2010).
Gastrointestinal decontamination techniques may be indicated for acute metal toxicities, although studies on their efficacy for this purpose are lacking and few consensus guidelines exist for their use in acute metal toxicity treatment. Gastric lavage (introduction of water into the stomach by a tube to wash out its contents) has been used in arsenic and lead poisonings (Tallis 1989; Rusyniak 2010; ATSDR 2007b; Caravati 2008). Emesis (induced vomiting) has also been suggested for removing metals within the stomach; however, some caustic metal compounds (mercuric oxide) may cause further damage by induced vomiting (ATSDR 2001), and emesis is not always effective for removing large amounts of solids (Manoguerra 2005). Bowel irrigation (introduction of water into the bowel to wash out its contents) may be useful for macroscopic particles of some metals (such as lead) that can easily transit through the intestines; larger particles may require surgery for removal (Roberge 1992; Rusyniak 2010; ATSDR 2007b). Activated charcoal may be effective for binding some ingested toxic metals or metal compounds (arsenic, thallium) but is ineffective for others (iron and mercury) (Worth 1984; Bateman 1999; Rusyniak 2002; Hoffman 2003; Rusyniak 2010; Manoguerra 2005).
Chelators enhance the elimination of metals (both toxic and essential) from the body. Their use to ameliorate metal toxicity has been validated by several human case reports and animal models. They are most often used in cases of acute intoxications; the efficacy of chelation therapy in chronic metal intoxication is less clear, as chelation therapies are more effective when administered close to the time of exposure (Jang 2011). The decision to chelate should be made by professionals with experience using chelation therapy, preferably in consultation with a poison control center or medical toxicologist (Adal 2013).
Chelators currently used in the United States include:
Dimercaprol (BAL). BAL is indicated for the treatment of acute lead encephalopathy in children and adults as well as acute inorganic arsenic or mercury toxicosis. It has also been used for chronic arsenic toxicity, but currently there are no guidelines to evaluate its effectiveness (ATSDR 2004; Jang 2011). BAL is given by intramuscular injection, often several times per day for a period of 5-10 days. Side effects include vomiting, excess salivation, watery eyes, runny nose, injection site pain, and possible chelation of essential trace metals if given for extended periods (Jang 2011).
DMPS. DMPS, an analog of dimercaprol (Bernhoft 2012), is an oral medication studied for arsenic and cadmium chelation in animal models (Aposhian 1984; Patrick 2003) and mercury chelation in mine workers (Bernhoft 2012). The dosage used in the human trial was 400 mg/day for 14 days. At the end of two weeks, DMPS significantly increased urinary excretion of mercury and improved toxicity symptoms; however, it did not alter blood mercury levels. Allergic rash was the only side effect noted.
Succimer (DMSA). DMSA is an oral medication used to treat mild-moderate lead toxicosis (acute or chronic) in children and adults as well as acute arsenic or mercury intoxication. For both lead and mercury intoxication in adults, DMSA is dosed at 10 mg/kg three times daily for 5 days, followed by 10mg/kg twice daily for 14 days. Side effects are mostly gastrointestinal (diarrhea and vomiting), metallic taste, and mild increase in liver enzymes; rash, chills, and decreased white cell counts have also (rarely) been reported (Jang 2011).
Prussian blue. Prussian blue is an oral chelator for thallium or cesium poisoning in adults and children; it is dosed 3 times per day. Side effects include constipation, abdominal pain, and a blue color of the stool (Jang 2011).
EDTA. Calcium-disodium EDTA is used to treat lead encephalopathy and moderate lead poisoning (Jang 2011; Born 2013). It is given by slow, continuous intravenous infusion. Side effects include malaise, headache, fatigue, chills or fever, myalgia, anorexia, nasal congestion, watery eyes, anemia, transient hypotension, clotting abnormalities, and kidney failure (Jang 2011). EDTA, particularly after prolonged treatment, can also chelate essential trace metals, such as zinc, copper, and manganese (Flora 2010). Sodium EDTA (without calcium) can cause life-threatening hypocalcemia (Brown 2006).
Penicillamine (Cuprimine®). Penicillamine has been used as an oral treatment for lead, mercury, and copper poisoning; its use has fallen out of favor due to its potential for serious complications, which include allergic reactions (seen particularly in people allergic to penicillin), a severe form of anemia, severe lowering of white blood cell counts, and kidney failure (Jang 2011).
Iron chelators. There are several iron chelators that have found use in the treatment of metabolic iron overload (hemochromatosis) as well as acute iron intoxication (such as iron supplement overdose). Deferoxamine mesylate (Desferal®) is an injectable iron chelator that can remove iron from abnormal tissue stores but not sites of active metabolic iron usage (such as transferrin or hemoglobin) (Sinicropi 2010). Side effects include skin rash, hypotension, respiratory distress, and eye/ear toxicity; acute neurological toxicity is also possible (Crisponi 2013; Sinicropi 2010). Oral iron chelators include Deferiprone (Ferriprox®) and Deferasirox (Exjade®). They have better distribution than deferoxamine, which also increases their toxicity (Heli 2011). Long term (6-month) deferoxamine treatment has been used to treat aluminum intoxication (Sinicropi 2010) and aluminum-related osteomalacia (Crisponi 2013).