How Should Patients Overexposed to Arsenic Be Treated and Managed?

Upon completion of this section, you will be able to

• identify primary strategies for treating arsenic-associated diseases.

Patients presenting to their primary care providers with a history of arsenic exposure will vary widely in their clinical condition.

• Some will be asymptomatic.
• Some will just be beginning to show signs of arsenic-associated disease, and others will have more established disease.
• The care provided, including any referrals made, will depend on the clinical status of the patient.
• Patients who demonstrate excessive occupational exposure (urinary arsenic greater than 35 microgram per liter) may benefit from early workplace intervention to prevent future hazardous exposure.

Gut decontamination and hemodynamic stabilization are key factors in the initial management of acute arsenic intoxication.

Patients with suspected acute arsenic poisoning generally require rapid stabilization with fluid and electrolyte replacement in an intensive care setting.

• Aggressive intravenous fluid replacement therapy may be life–saving in severe poisoning.
• Gastric lavage may be useful soon after an acute ingestion to prevent further absorption.
• The efficacy of activated charcoal is controversial, but its administration together with a cathartic (such as sorbitol) is frequently recommended.
• If profuse diarrhea is present, cathartics should be withheld.
• Hemodialysis may be beneficial in a patient with concomitant renal failure.

Chelating agents administered within hours of arsenic absorption may successfully prevent the full effects of arsenic toxicity.

Dimercaprol (2, 3 dimercaptopropanol, also known as British anti Lewisite or BAL), was previously the most frequently recommended chelating agent for arsenic. The currently recommended treatment is 2-3-dimercapto-1-propanesulfonate (DMPS) or meso 2, 3-dimer-captosuccinic acid (DMSA). These are more water soluble than BAL, and can be administered orally with lower toxicity [Mazumder et. al. 2001].

All known chelating agents have adverse side effects and should be used with caution.

• In animal models, the efficacy of chelation therapy generally declines as the time elapsed since exposure increases.
• If patients are treated within several hours after arsenic ingestion, chelation is likely to be beneficial. Therefore, even if arsenic ingestion is only suspected, but not confirmed, consultation with a clinical specialist with expertise in the treatment and management of arsenic poisoning is key.

Data supporting duration of treatment are limited, and regimens may warrant adjustment. If acute renal insufficiency develops, hemodialysis may be of value.

If the source of arsenic exposure has not been determined, the patient may be at risk for further arsenic intoxication.

Identification and removal of the toxic source and supportive measures are primary concerns for the treatment of chronically exposed patients.

• Studies suggest that the use of vitamin A analogs (retinoids) may be useful in treating pre-cancerous arsenical keratoses [Elmariah et al. 2008].
• Recovery from chronic arsenic toxicity, particularly from the resulting peripheral neuropathy, may take months and may not be complete.
• An established arsenical neuropathy is not improved by chelation therapy.
• Significant improvement of symptoms and signs of chronic arsenic poisoning has been demonstrated in a prospective single blind, placebo-controlled trial with DMPS [Mazumder et al. 2001].

Patients demonstrating excessive exposure on urine testing or clinical effects of arsenic exposure, and whose source of exposure is unclear, may require environmental testing (such as of drinking water), attention to exposure from malicious intent, or workplace investigation.

After an intervention has been made, follow-up urine testing may be necessary to confirm a reduction in exposure, and follow-up clinical testing may be necessary to verify a resolution of clinical and lab test abnormalities.

Patients whose excessive arsenic exposure occurred in the workplace can be medically removed from exposure while remediation of the workplace is undertaken.

• This requires prompt notification of the employer of a hazard that requires corrective action.
• Often an industrial hygienist familiar with the industrial processes can be consulted by the employer.
• If an imminent hazard exists that the employer has not addressed, the Occupational Safety and Health Administration (OSHA) can require the employer to take appropriate corrective action. OSHA is the federal regulatory agency responsible for enforcing federal workplace health standards.

OSHA’s standard for arsenic also requires that medical examinations be provided for all employees exposed to levels of inorganic arsenic above the action level of 5 micrograms per meter cubed for at least 30 days per year. For more information on the OSHA standard for arsenic, see http://www.osha.gov/SLTC/arsenic/index.html

Nutritional status may play a role in preventing arsenic health effects. For example, arsenic and selenium may be mutually antagonistic [Zeng et al. 2005]. There have been recent reports that a diet rich in selenium and other antioxidants (such as vitamin E) helps promote methylation of arsenic which leads to increased excretion [Verret et al. 2005; Rossman 2007; Son et al. 2008]. Methyl donors such as folate may also be of help in arsenic metabolism and excretion in humans [Rossman 2007]. Arsenic-induced disease has been shown to increase in individuals who are mal- or under-nourished, possibly due to the decrease in arsenic methylation [Hsueh et al. 1995; Mitra et al. 2004; Steinmaus et al. 2005].

Arsine gas poisoning requires careful monitoring of hematocrit/hemoglobin and renal function.

• Therapy is supportive and is primarily aimed at maintaining renal function. Red cell transfusion may be necessary to replace the patient’s hemolyzed red cells.
• Patients with significant hemolysis may require folate or iron supplementation.

• Most frequently, removal from exposure is the key management intervention for arsenic effects due to overexposure.
• Gut decontamination and hemodynamic stabilization are key factors in the initial management of acute arsenic intoxication.
• In severe acute arsenic over exposure such as heavy ingestion, chelation with DMSA or DMPS may reduce morbidity. This should be done in consultation with a clinical expert in arsenic poisoning treatment.
• Patients occupationally over exposed to arsenic may want to discuss with employers their concerns regarding ways to prevent this hazardous exposure.
• Arsine gas poisoning requires careful monitoring of hematocrit/hemoglobin and renal function.