Hemodynamic stabilization and gut decontamination are key factors in the initial management of acute arsenic intoxication.
Be certain that appropriate decontamination of the patient has been carried out. Remove and double-bag contaminated clothing and all personal belongings (ATSDR 2000b).
Quickly assess for a patent airway, and ensure adequate respiration and pulse. Maintain adequate circulation (ATSDR 2000b). Consult with the regional poison control center for advice regarding arsenic poisoning and appropriate treatment.
Wash exposed skin and hair with mild soap and water, and rinse thoroughly with water (ATSDR 2000b). Use caution to avoid hypothermia, particularly with children and the elderly (ATSDR 2000b).
Flush exposed or irritated eyes with plain water or saline for at least 15 minutes (ATSDR 2000b). Remove contact lenses if easily removable without additional trauma to the eye (ATSDR 2000b).
Do not induce emesis (ATSDR 2000b). The effectiveness of activated charcoal is questionable, but administration of activated charcoal as an aqueous slurry in persons who are awake and able to protect their airway is recommended pending further evaluation in cases of ingestion of unknown quantities (ATSDR 2000b). Activated charcoal is most effective when administered within 1 hour of ingestion (ATSDR 2000b; Anonymous 1999a). At 1 gram per kilogram (gm/kg), the usual adult dose is 60-90 grams (g), and the child dose is 25-50 g. A soda can and straw may be of assistance when offering charcoal to a child (ATSDR 2000b). Complications include emesis and aspiration (Anonymous 1999a).
Persons with evidence of significant exposure and all persons who have ingested arsenic trioxide should be transported to a medical facility for evaluation.
Evaluate and support the airway, breathing, and circulation as appropriate.
Establish intravenous access in symptomatic patients and monitor cardiac rhythm (ATSDR 2000b). Persons with acute arsenic poisoning usually die from hypovolemic shock secondary to vomiting, diarrhea, gastrointestinal bleeding, and capillary leaking (third-spacing of fluids) (Anonymous 1999a). Fluid replacement and transfusion of blood products as required are the mainstays of initial treatment, and should begin as soon as possible, even in the absence of hypotension initially (Anonymous 1999a, 2000). Volume status should be monitored carefully and a brisk urine output should be maintained. Bladder catheterization, central venous catheter, or a Swan-Ganz catheter should be used as clinically warranted (Anonymous 1999a, 2000). Pressors should be considered only if fluid replacement does not reverse the hypotension (Anonymous 2000).
Do not induce emesis (ATSDR 2000b). In cases of recent ingestion (<1 hour earlier), and if spontaneous emesis has not occurred, consider performing gastric lavage to prevent further absorption (ATSDR 2000b). Seizure control and appropriate airway protection are mandatory before gastric lavage (Anonymous 1999a). Insert an orogastric tube and begin lavage with water or normal saline as soon as possible (ATSDR 2000b). Continue lavage until the return is clear (ATSDR 2000b). The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance (Anonymous 1999a). Caution should be used with children and the elderly to avoid hypothermia and electrolyte imbalance (Anonymous 1999a). Complications include aspiration pneumonia; hypoxia; hypercapnia; and mechanical injury to the throat, esophagus, or stomach (Anonymous 2000).
Activated charcoal may not bind significant amounts of arsenic and may not be of therapeutic value (Kersjes et al. 1987; Al-Mahasneh and Rodgers 1990), but should be considered within 1 hour of ingestion until definitive quantitative data are available (ATSDR 2000b; Anonymous 1999a, 2000). Complications include emesis and aspiration (ATSDR 2000b; Anonymous 1999a, 2000).
An abdominal radiograph should be obtained in all persons ingesting arsenic, because it is radiopaque (ATSDR 2000b; Anonymous 1999a, 2000). If a radiograph demonstrates arsenic in the lower GI tract, whole-bowel irrigation should be considered (e.g., with a polyethylene glycol electrolyte lavage solution) (ATSDR 2000b; Anonymous 1999a; Mitchell et al. 1989). This procedure should not be used in persons who are at risk for becoming obtunded, comatose, or seizing until the airway is secure (Anonymous 1999a). Repeat abdominal films as necessary to ensure that gastric emptying maneuvers have been effective (Anonymous 2000).
A chest radiograph should also be obtained because pulmonary edema may occur (Anonymous 2000).
Maintain a brisk urine output and consider alkalinization of the urine (pH 7.5) to protect the kidneys from deposition of red cell breakdown products (ATSDR 2000b; Anonymous 1999a). Assure adequate renal function before administering sodium bicarbonate (ATSDR 2000b).
Chelating agents administered within hours of arsenic absorption may successfully prevent the full effects of arsenic toxicity.
Chelation therapy may curtail the distribution of arsenic in the body and reduce the body burden (ATSDR 2000b). However, as time increases after exposure, chelation therapy becomes less effective in reducing the severity of poisoning and in reducing the risks of delayed effects (ATSDR 2000b). In addition, chelation therapy can cause significant adverse effects (ATSDR 2000b; Anonymous 1999a). As a result, the decision to chelate a patient should be made only by professionals experienced in the use of chelation, preferably in consultation with a regional poison control center or a clinical toxicologist (ATSDR 2000b). Hospitalize and monitor patients who receive chelation therapy (ATSDR 2000b; Anonymous 1999a).
The 24-hour urine arsenic level is useful for monitoring patients. Normal levels are <50 micrograms/liter (µg/L) in the absence of recent consumption of seafood that contains organic forms of arsenic (ATSDR 2000b). A chelated or nonchelated urine level >100 µg/L is usually considered abnormal (ATSDR 2000b).
Asymptomatic patients should not be chelated without the guidance of a 24-hour urinary arsenic level (ATSDR 2000b). The urine arsenic level that should prompt consideration of chelation in an asymptomatic patient has been recommended as 200 µg/L (Lee et al. 1995).
Patients with a clear history of exposure to arsenic with significant cardiovascular and/or GI symptoms may require chelation before laboratory confirmation of the 24-hour urinary arsenic level (ATSDR 2000b). In this case, a high blood arsenic level (normal defined as <7 µg/100 dL) may confirm the diagnosis (ATSDR 2000b). However, because arsenic moves quickly out of the bloodstream (its initial half-life in blood is 1 to 2 hours), a normal value does not necessarily exclude poisoning (ATSDR 2000b). If the blood arsenic level is normal, but the 24-hour urinary arsenic level is elevated, and there are compatible clinical symptoms, the diagnosis can still be made (ATSDR 2000b).
In acutely symptomatic patients, the agent most frequently recommended is dimercaprol, also known as BAL (British anti-Lewisite) (ATSDR 2000b; Anonymous 1999a, 2000). Parenteral dimercaprol is administered intramuscularly at 3 to 5 mg/kg of body weight every 4 to 12 hours until symptoms resolve or another chelator is substituted (Anonymous 1999a, 2000). The dose and frequency is dependent and adjusted based on the severity of the patient's exposure and symptoms and the urinary arsenic levels (ATSDR 2000b; Anonymous 1999a, 1999b, 2000). Higher doses invariably cause adverse effects, including hypertension, tachycardia, anorexia, restlessness, pain, vomiting, salivation, fever, seizures, "leukotoxic effect," and reducing substances in the urine (ATSDR 2000b; Anonymous 1999a, 1999b, 2000; Woody and Kometani 1948).
In studies of the efficacy of dimercaprol, treatment with dimercaprol has resulted in clinical improvement and a decrease in hospital days in children poisoned with arsenic (Woody and Kometani 1948). It has also been reported to effect complete recovery in a woman and her 20-week fetus after an acute ingestion of inorganic arsenic by the woman (Daya et al. 1989). In one study of 307 persons after acute sodium arsenite poisoning, all subjects in all dimercaprol treatment groups (including 246 persons who were given no dimercaprol) were free of arsenic-related symptomatology at 1- or 2-year follow-up (Roses et al. 1991). In animal studies, dimercaprol has reduced the organ deposition of arsenic in a rabbit model (Snider et al. 1990).
Contraindications to dimercaprol include pregnancy, preexisting renal disease, concurrent use of medicinal iron, and glucose-6-phosphate dehydrogenase deficiency (ATSDR 2000b).
Chelation therapy should be continued until the 24-hour urinary arsenic level falls below 50 µg/L (Goldfrank et al. 1986; American Medical Association 1986). Observation for the return of symptoms is encouraged (Anonymous 2000).
Oral agents such as 2,3-dimercaptosuccinic acid (DMSA, Succimer), or D-penicillamine have been used as alternatives to BAL. DMSA is approved for the treatment of
pediatriclead poisoning in the United States (ATSDR 2000b; Anonymous 2000). It appears to be an effective chelator of arsenic in experimental animals (Graziano et al. 1978) and humans (Lenz et al. 1981; Kosnett and Becker 1987; Fournier et al. 1988). It has been efficacious in pediatric arsenic poisoning (Cullen et al. 1995).
DMSA has a safety ratio of 20 times greater than BAL. Because the total dosage of BAL is limited by its intrinsic toxicity, the greater safety ratio of DMSA allows for longer and more prolonged dosing of DMSA (Inns and Rice 1993). As a result, DMSA is often substituted for BAL when the patient's condition improves, or when the patient has renal disease (ATSDR 2000b). The recommended dose is 10 mg/kg or 350 milligrams/square meter every 8 hours for 5 days, followed by 10 mg/kg every 12 hours for 14 days (Anonymous 2000, 1991). DMSA has a sulfurous odor, which may be evident in the patient's breath and urine, and adverse effects include rash, nausea, vomiting, diarrhea, transient increase in liver function tests, and thrombocytosis (Anonymous 2000, 1991).
The use of D-penicillamine as an oral chelating agent is controversial (ATSDR 2000b). It has been used successfully in acute arsenic poisoning in children (Peterson and Rumack 1977; Kuruvilla et al. 1975; Watson et al. 1981), but in an experimental animal model, D-penicillamine was found to lack effectiveness (Kreppel et al. 1989). It should be avoided in patients who are allergic to penicillin (ATSDR 2000b; Anonymous 2000).
Available evidence does not support routine use of chelation therapy for patients with an established arsenic neuropathy.
BAL has been used for the treatment of chronic arsenic poisoning, but there are no established biologic criteria or measures of effectiveness.
When the arsenic exposure has been chronic environmental exposure, removing the patient from the source of exposure may be beneficial. Children with elevated urinary arsenic concentrations above normal had a substantial reduction in arsenic concentrations after moving away from an area where the soil had been contaminated by a smelter (Anonymous 1987, 1999b).
