1) Ingestion can cause severe irritation of the mouth, throat, esophagus, and stomach. Laryngeal or tracheal edema may occur and compromise the airway. Severe esophageal erosions may be seen in ingestions. Direct dermal exposure can cause irritation and blistering. Following inhalation, ingestion, or dermal exposure, arsenic is absorbed systemically and arsenic poisoning results.

1) ADMINISTER MILK (preferred) OR WATER (one or two glassfuls) to dilute the hydrofluoric acid in the oropharynx, esophagus and stomach. Milk provides calcium ions which will bind the fluoride ion and decrease the penetrability.

1) Because of the corrosive effects of hydrofluoric acid released following contact with moisture, EMESIS should NOT be induced.

1) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
2) There may be slow absorption of ingested arsenic trichloride and lavage may be effective even after several hours.
3) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.

1) Consider nasogastric suction or lavage with a soft tube in patients with significant ingestions who present within 90 minutes of exposure and have not spontaneously vomited. Calcium gluconate 10 percent may be added to the lavage fluid.

1) As there is little risk in using activated charcoal, it is recommended until further data are available.
2) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.

1) ADMINISTER MILK OF MAGNESIA after oral dilution with milk or water, for its soothing effect.

1) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.

1) Monitor liver, renal and cardiac functions. Maintain high urine output.

1) red cell breakdown products from hemolysis in the renal tubules.

1) Administer 1 to 2 mEq/kg sodium bicarbonate bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. Adjust as needed to achieve a urine pH of at least 7.5 and a urine output of 1 to 3 mL/kg/hr.
2) Assure adequate hydration and renal function. Monitor fluid balance, serum electrolytes, and blood pH. Obtain hourly intake/output and urine pH.

1) DIMERCAPROL (BAL) - Usual dosage range is 3 to 5 milligrams/kilogram intramuscularly every 4 to 12 hours until symptoms resolve or another chelator is substituted. The dose and frequency used depend on the degree of toxicity seen. Dose dependent side effects may occur.
2) D-PENICILLAMINE - The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day; adults may require larger doses (ie, up to 2 grams/day).
3) DMSA - 2,3-Dimercaptosuccinic acid (DMSA) is an investigational drug. It has the advantage of being an oral agent as well as being relatively non-toxic.
4) N-acetylcysteine (NAC) cannot presently be recommended for the treatment of arsenic poisoning.
5) THERAPEUTIC END-POINT - Repeat five-day courses of chelation therapy should be prescribed in severe poisonings until the 24-hour urine arsenic level falls below 50 micrograms/liter.

1) Institute continuous cardiac monitoring, obtain an ECG, and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders. Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Because arsenic can cause torsades de pointes and QTc prolongation, amiodarone should only be used with extreme caution. Unstable rhythms require immediate cardioversion.

1) Treat with magnesium; atrial overdrive pacing may also be necessary. Correct electrolyte abnormalities.

1) URINE ALKALINIZATION

1) DIMERCAPROL (BAL) - Usual dosage range is 3 to 5 milligrams/kilogram intramuscularly every 4 to 12 hours until symptoms resolve or another chelator is substituted. The dose and frequency used depend on the degree of toxicity seen. Dose dependent side effects may occur.
2) D-PENICILLAMINE - The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day, adults may require larger doses (ie, up to 2 grams/day).
3) DMSA - 2,3-Dimercaptosuccinic acid (DMSA) is an investigational drug. It has the advantage of being an oral agent as well as being relatively non-toxic.
4) N-acetylcysteine (NAC) is not presently recommended for the treatment of arsenic poisoning.
5) THERAPEUTIC END-POINT - Repeat five-day courses of chelation therapy should be prescribed in severe poisonings until the 24-hour urine arsenic level falls below 50 micrograms/liter.

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
3) Treatment of CHEMICAL BURNS may be required. Refer to TREATMENT/DERMAL EXPOSURE section in the main body of this document for more information.
4) Alkalinization of the urine may prevent deposition of red cell breakdown products from hemolysis in renal tubular cells.
5) Chelation therapy may be indicated at a urine arsenic level of 200 mcg/liter or higher. Dimercaprol (BAL), D-PENICILLAMINE and DMSA are effective arsenic chelators.
6) A MOBILIZATION TEST - has been suggested to aid the diagnosis of mild or chronic exposure. Its usefulness has been questioned because of the relatively rapid excretion of absorbed arsenic. Refer to TREATMENT/DERMAL EXPOSURE section in the main body of this document for more information.
7) Physical therapy may be helpful for patients with established arsenical neuropathies.
8) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
9) HEMODIALYSIS - should be performed in the presence of any degree of renal failure.
10) Restriction from further exposure may be necessary for workers with significant arsenical dermatitis, ulcerations, or dermatoses.
11) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.

1) Particularly ventricular tachycardia and ventricular fibrillation (with QT prolongation) have been described after acute arsenic ingestion (Peterson & Rumack, 1977; Goldsmith, 1980; St Peter et al, 1970).

1) ECG changes have included QT prolongation, left axis deviation, peaked T waves, and also deeply inverted T waves (Gousios & Adelson, 1959; Heyman et al, 1956).

1) Laryngeal or tracheal edema may occur and compromise the airway (Delepine, 1923).

1) Inhalation of arsenic trichloride fumes can cause irritation of the respiratory tract, and could result in bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema, as well as systemic arsenic poisoning (EPA, 1985; Sax & Lewis, 1987; AAR, 1987).

1) Either noncardiogenic from capillary leaking, or cardiogenic from myocardial depression, may occur and be life-threatening (Morgan, 1989).

1) Acute respiratory failure, presumably from severe weakness of respiratory muscles, has been seen in a patient with severe arsenic poisoning (Greenberg et al, 1979). The condition progressed despite dimercaprol therapy and required ventilatory assistance for one month.

1) Adult respiratory distress syndrome (ARDS) has been reported (Zaloga et al, 1970; Schoolmeester & White, 1980).

1) Toxic delirium and encephalopathy are complications of acute arsenic poisoning (Jenkins, 1966).

1) Peripheral neuropathy is common after acute arsenic poisoning. After acute exposure, it commonly begins one to 3 weeks later (Le Quesne & McLeod, 1977; Heyman et al, 1956). It usually begins as paresthesias of the soles of the feet, then the hands, progressing proximally over the next few days (Heyman et al, 1956).
2) Severe muscle weakness and wasting then develops, causing severe disability (Le Quesne & McLeod, 1977). It may initially be confused with Guillain-Barre syndrome (Donofrio et al, 1987). The paresthesias may be painful and are frequently described as severe burning pain in a stocking and glove distribution (Harbison, 1998).
3) PHYSICAL FINDINGS of arsenic neuropathy usually include prominently decreased sensation to touch, pinprick, and temperature, frequently in a stocking and glove distribution (Heyman et al, 1956). Loss of vibration sense is also common. Profound muscle weakness and wasting, distal more so than proximal, is also seen (Donofrio et al, 1987; Heyman et al, 1956). Wrist drop, foot drop, and fasciculations may be seen (Heyman et al, 1956).
4) ELECTRODIAGNOSTIC STUDIES of arsenic neuropathy have shown a reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials (Le Quesne & McLeod, 1977).
5) NERVE BIOPSY may demonstrate various stages of axonal degeneration without demyelination (Le Quesne & McLeod, 1977) or with demyelination (Donofrio et al, 1987).
6) DIMERCAPROL (BAL) does not seem to be able to reverse arsenic neuropathy (Donofrio et al, 1987; Heyman et al, 1956; Le Quesne & McLeod, 1977); recovery is usually very slow and incomplete. However, it has been claimed that if BAL is administered within hours of ingestion, neuropathy may be prevented (Jenkins, 1966), although this may not always be true (Marcus, 1987).

1) Ingestion can cause severe irritation of the mouth, throat, esophagus, and stomach (CHRIS , 2000; EPA, 1985).

1) Severe esophageal erosions may be seen in ingestions (HSDB , 2000).

1) Early symptoms within hours following arsenic ingestion include abdominal pain, vomiting, profuse bloody or watery diarrhea (sometimes described as "rice-water-like") (Gilman et al, 1985; Hathaway et al, 1996; Harbison, 1998), pain in the extremities and muscles, weakness, and flushing of the skin (HSDB , 2000; Sittig, 1991).

1) Hepatocellular damage may occur after acute arsenic poisoning, but is not common (Donofrio et al, 1987). Mitotic activity of hepatocytes may be a common post-mortem finding in arsenic poisoning (Mackell et al, 1985).

1) Anuria, hematuria, proteinuria (Zaloga et al, 1970; Schoolmeester & White, 1980), acute tubular necrosis, renal failure (Giberson et al, 1976; Vaziri et al, 1980), and chronic renal insufficiency from cortical necrosis have been described (Gerhardt et al, 1978).

1) Hemolysis may occur after acute arsenic poisoning (Kyle & Pease, 1965).

1) After either acute or chronic arsenic exposure, pancytopenia may be seen (Kyle & Pease, 1965; Kjeldsberg & Ward, 1972). However, isolated leukopenia or anemia may also be seen. The anemia is usually normochromic and normocytic, but may be hypochromic and microcytic (Kyle & Pease, 1965).
2) Bone marrow aspirate may demonstrate pronounced erythroid hyperplasia similar to that seen with pernicious anemia (Selzer & Ancel, 1983). Basophilic stippling and rouleau formation of red cells may also be seen (Kyle & Pease, 1965).

1) The fumes are very irritating to the skin (AAR, 1987; Sax & Lewis, 1987; EPA, 1985; Grant, 1986; Sittig, 1991).

1) Direct dermal exposure can cause irritation and blistering (EPA, 1985).

1) Following inhalation, ingestion, or dermal exposure, arsenic is absorbed systemically and arsenic poisoning may occur (EPA, 1985; HSDB , 2000; Delepine, 1923).

1) Common skin findings after either acute or chronic arsenic poisoning may include flushing, diaphoresis, palmar hyperkeratosis, peripheral edema, hyperpigmentation, brawny desquamation (Heyman et al, 1956), and exfoliative dermatitis (Zaloga et al, 1970; Schoolmeester & White, 1980; Hutton & Christians, 1983).

1) Transverse white striae of the nails may be seen after acute exposure. Mee's lines commonly take 5 weeks to appear above the cuticle and advance 1 mm per week afterwards, allowing an approximation of the time of acute exposure (Heyman et al, 1956).

1) Shingles may also be a complication of arsenic poisoning (Jenkins, 1966; HSDB , 2000).

1) There is little evidence supporting the teratogenic potential of arsenic compounds in humans (Schardein, 1993). While arsenic is likely fetotoxic in humans, data are currently inadequate to determine whether or not such effects could occur in the absence of maternal toxicity (Council on Scientific Affairs, 1985).
2) One study revealed increased rates of spontaneous abortion and decreased birth weights of offspring in women living close to a smelter in Sweden that emitted arsenic, lead, and sulfur dioxide. In this study, there was no increased incidence of congenital malformations (Schardein, 1993).

1) Sodium arsenite has caused teratogenic and embryotoxic effects in the offspring of pregnant mice, rats, and hamsters when administered orally or parenterally (Schardein, 1993; Council on Scientific Affairs, 1985; Hood, 1972; Baxley et al, 1981). In some hamster experiments, no teratogenic effects were noted (Schardein, 1993; Hood & Harrison, 1982).
2) The route of arsenic administration proved to have a significant influence on teratogenic effects in mice. An oral dose three times that of the intraperitoneal dose was required to induce the same fetal effects (HSDB , 2000).
3) At doses of 10 or 12 mg/kg administered intraperitoneally to mice on days 7 through 12 of gestation, sodium arsenite caused increased fetal deaths, decreased fetal weights, and developmental abnormalities including exencephaly, micrognathia, open eyes, tail abnormalities, fused ribs, and fused or missing vertebral ossification centers (Hood, 1972).
4) High doses of intravenous or intraperitoneal arsenic produced teratogenic effects including exencephaly, genitourinary system defects, and skeletal defects in hamsters, rats, and mice (Proctor et al, 1988; Hathaway et al, 1996; HSDB , 2000). At lower doses in drinking water, only minimal fetal effects have been seen (Proctor et al, 1988; Hathaway et al, 1996).
5) In a cultured mouse embryo system sodium arsenate and arsenite were both teratogenic, resulting in abnormalities of cranial closure, abnormalities of the eye and optic nerve, and pharyngeal arch defects. The ED50 for arsenate was about threefold higher than that for arsenite (Tabocova et al, 1996)

1) NEONATAL DEATH - Acute ingestion of arsenic in a female with a 30 week pregnancy has been reported to result in the death of the infant born 4 days after the poisoning (Lugo et al, 1969). The child apparently died of hyaline membrane disease, but did have elevated tissue levels of arsenic. It seems apparent that arsenic can cross the placenta.
2) Six women developing arsenical encephalopathy during the fourth to eighth months of pregnancy delivered normal children (Schardein, 1993).
3) In studies of a population in Argentina exposed to environmental arsenic (drinking water arsenic approximately 200 mcg/L), cord blood concentrations (median 9 mcg/L) were almost as high as maternal blood concentrations (median 11 mcg/L). Essentially all of the blood arsenic and about 90 percent of the urinary arsenic in both mothers and newborns was in the form of dimethylarsinic acid in comparison to 70 percent in the urine of non-pregnant women, suggesting that the methylation of arsenic may be up-regulated during pregnancy (Concha et al, 1998).
4) Increased rates of spontaneous abortions and decreased birth weights in the offspring were found in a study of women living near a smelter in Sweden which emitted lead, sulfur dioxide, and arsenic. There was no increased incidence of congenital malformations in this group (Schardein, 1993). The significance of this study to pure chronic arsenic exposure during pregnancy is unclear.

1) There is evidence that some arsenic compounds cross the placenta in mammals (HSDB , 2000; Barlow & Sullivan, 1982).

1) Arsenic is excreted in the breast milk in both experimental animals and humans (HSDB , 2000; Barlow & Sullivan, 1982). Nursing infants exposed to arsenic in milk may encounter problems in later brain development (Barlow & Sullivan, 1982).

1) Continuous dietary administration of up to 215 mg/kg of arsenic did not have adverse effects on fertility in female rats (Barlow & Sullivan, 1982).

1) Not Listed

1) The EPA and IARC have classified inorganic arsenical compounds as Class A carcinogens based on sufficient human epidemiological evidence (EPA, 1988; Hathaway et al, 1996; HSDB , 2000). Although arsenic compounds are well-established as human carcinogens, few animal studies show such effects (Clayton & Clayton, 1994).
2) Chronic arsenic poisoning from arsenic trichloride produces cancerous skin changes, and an increased risk of lung cancer (Morgan, 1993; Lewis, 1996; Baselt, 2000; HSDB , 2000).
3) There is consistent evidence linking excesses of respiratory cancers to occupational arsenic exposure (ACGIH, 1996). In occupational settings, lung cancer mortality has been related to intensity rather than duration of exposure to arsenic. In a large cohort study of workers involved in the production and use of arsenical pesticides, those workers with the highest estimated exposure levels had a ninefold increase in respiratory cancer mortality (Hathaway et al, 1996).
4) Nonworker populations living near emission sources of arsenic to air may also have increases in lung cancer, but studies to date have not been definitive (HSDB , 2000).
5) In additional, environmental exposure studies in various regions where arsenic exposure is endemic, recent epidemiologic studies have suggested possible relationships of arsenic exposure to cancers of the lung (Hopenhayn-Rich et al, 1998; Smith et al, 1998), kidney (Hopenhayn-Rich et al, 1998), and bladder (Smith et al, 1998; Hopenhayn-Rich et al, 1996).
6) Bone structure and lung cancers are the two primary sites observed as a result of arsenic exposure. Although tumors of the lung and face also predominate, other cancer sites include the scrotum, buttocks, abdomen, clavicle and lower chest (HSDB , 2000).
7) A study of a population in Taiwan drinking high-arsenic concentration artesian well water found a dose-response relationship between the amount of arsenic in the water and the incidence of mortality from skin, lung, kidney, liver, prostate, and bladder cancers (HSDB , 2000) ACGIH, 1996; (Chen et al, 1988; Hathaway et al, 1996).
8) One theory suggests that arsenic compounds are not direct carcinogens, but act instead as indirect, gene-inducing carcinogens that activate oncogenic virus in humans (Hathaway et al, 1996).
9) SKIN CARCINOMA - Basal cell and squamous cell carcinomas of the skin have been described after both acute (Renwick et al, 1981) and chronic (Jackson & Grainge, 1975; Wagner et al, 1979; HSDB , 2000) arsenic exposure. Two patients with arsenic-induced basal cell carcinomas of the skin also developed malignancies of other organs (breast and colon) (Jackson & Grainge, 1975).
10) Skin cancer in humans is causally associated with exposure to inorganic arsenic compounds in drinking water, the occupational environment, and drugs (Sittig, 1991; Hathaway et al, 1996). Three distinct skin cancers, Bowen's disease, basal cell carcinoma, and squamous cell carcinoma, have been associated with chronic exposure. These carcinomas are thought to develop secondary to arsenical keratoses, which manifest as small, cornlike lesions that are benign but may become precancerous (Harbison, 1998) Raffle, 1994).
11) HEPATIC CARCINOMA - One worker who was exposed to arsenious oxide and sodium arsenite for 20 years developed cirrhosis of the liver and primary liver carcinoma (Finkel, 1983).

1) An arsenic blood level below 7 mcg/100 mL is considered in the normal range. Blood levels are highly variable and may be useful only after acute exposure to confirm the diagnosis; they may become undetectable following acute poisoning at times when urinary arsenic excretion remains substantial (Fesmire et al, 1988).
2) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.
3) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
4) This agent may cause nephrotoxicity. Monitor renal function tests and urinalysis in patients with significant exposure.
5) Monitor serum electrolytes in patients with significant vomiting, diarrhea, or hypotension from fluid "third spacing."

1) Monitor arterial blood gases in patients who develop pulmonary edema.

1) 24-hour urine collections for total arsenic excretion or spot specimens measured as concentration of arsenic (in micrograms or milligrams) per gram of urinary creatinine are generally the preferred samples, as they balance out the effects of varying urine volume and concentration.
2) A method for a quick urine spot test (Reinsch test) has been described (Grande et al, 1987) but its clinical utility is uncertain. Even with chelation, an unexposed individual should not have more than 100 mcg of arsenic per 24 hour total urine output. Urinary arsenic may be elevated up to 200 to 1700 mcg/L within 4 hours after eating some seafoods (Baselt, 2000; Baselt, 1988; Proctor et al, 1988).

1) HAIR

a) Esophagrams in the acute and subacute phase demonstrate edema, hemorrhage, ulcerations, atony, and dilation. Strictures of the esophagus were present in the chronic phase. These radiographic findings are not different from those found in alkaline corrosive esophagitis (Muhletaler, 1980).

1) ADMINISTER MILK (preferred) OR WATER (one or two glassfuls) to dilute the hydrofluoric acid in the oropharynx, esophagus, and stomach. Milk provides calcium ions which will bind the fluoride ion and decrease the penetrability.

1) Because of the corrosive effects of hydrofluoric acid released following contact with moisture, EMESIS should NOT be induced.

1) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
2) There may be slow absorption and lavage may be effective even after several hours.
3) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
4) PRECAUTIONS:
5) LAVAGE FLUID:
6) COMPLICATIONS:
7) CONTRAINDICATIONS:

1) There are no reports of activated charcoal being used; however, as there is little risk in using activated charcoal, it is recommended until further data are available.
2) CHARCOAL ADMINISTRATION
3) CHARCOAL DOSE

1) Hypotension from acute arsenic ingestion is likely due to intravascular volume depletion from vomiting, diarrhea, or third spacing of fluids.
2) The initial treatment should consist of adequate volume replacement with crystalloid or blood products. Placing the patient in Trendelenburg and using MAST trousers may also be useful.
3) Aggressive monitoring of volume status should be undertaken even in the absence of hypotension initially. Bladder catheterization to monitor hourly urine output, a central venous catheter, or a Swan-Ganz catheter should be used as clinically warranted.
4) Pressors should be used only if volume replacement does not reverse the hypotension.
5) DOPAMINE
6) NOREPINEPHRINE

1) Tachycardia may be a response to hypovolemia and should be treated initially with fluid replacement as clinically warranted.

1) VENTRICULAR DYSRHYTHMIAS SUMMARY
2) LIDOCAINE
3) AMIODARONE

1) SUMMARY
2) MAGNESIUM SULFATE
3) OVERDRIVE PACING
4) POTASSIUM REPLETION
5) ISOPROTERENOL
6) OTHER DRUGS
7) AVOID

1) Alkalinization of the urine may help prevent deposition of red cell breakdown products in renal tubular cells if hemolysis is occurring.
2) SODIUM BICARBONATE/INITIAL DOSE
3) SODIUM BICARBONATE/REPEAT DOSES
4) CAUTION

1) INDICATIONS
2) THERAPEUTIC ENDPOINT
3) MOBILIZATION TEST

1) Dimercaprol (BAL) is an effective arsenic chelator but has the disadvantages of requiring painful intramuscular injections and having numerous side effects.
2) DOSE: The dose used is dependent on the severity of the patient's symptoms and the urinary arsenic levels.
3) EFFICACY

1) DOSE: The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day (Peterson & Rumack, 1977), but larger doses may be required in adults.
2) ADVERSE EFFECTS: Long term therapy for the treatment of arthritis or Wilson's disease has resulted in fever, pruritus, leukopenia, thrombocytopenia, eosinophilia, and renal toxicity, but this has not been reported when the drug is used short term for heavy metal chelation.
3) EFFICACY

1) EFFICACY

1) EFFICACY

1) N-ACETYLCYSTEINE - N-acetylcysteine (NAC) has been shown to increase the LD50 of mice poisoned with sodium arsenite (Shum et al, 1981). NAC has the advantage of being both an oral and an intravenous agent, and so may become the only chelator which can be given intravenously for acute arsenic poisoning.
2) METHYL GROUP DONORS - Sulfo-adenosyl-L-methionine (Samyr(R), Bio-research, Milan) has been proposed as an agent which may promote methylation and subsequent urinary elimination of arsenic (Mahieu et al, 1987).

1) Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy (Jenkins, 1966). However, once neuropathy has developed (usually 1 to 3 weeks after acute exposure), chelation with BAL may not be effective in reversing it (Heyman et al, 1956; Donofrio et al, 1987; Le Quesne & McLeod, 1977).

1) IMMUNOTHERAPY - Use of immunotherapy for the treatment of sodium arsenite toxicity is being investigated in animal models. Leikin et al (1991) demonstrated a protective effect of anti-arsenic reactive serum female balb/c mice. Applicability of immunotherapy to treatment of human poisonings has not been determined.
2) 2,3-DITHIOERYTHRITOL - Is a synthesized derivative of BAL. Preliminary laboratory evidence indicates that it is less toxic than BAL or DMSA (Boyd et al, 1989).

1) MELARSOPROL ENCEPHALOPATHY - Only 4 percent of those patients given corticosteroids (prednisolone, not more than 40 milligrams daily) developed melarsoprol encephalopathy compared to approximately 33 percent in those patients receiving no steroids in a prospective randomized trial involving 600 patients with parasitology-confirmed Trypanosoma brucei gambiense infections (Pepin et al, 1989).

1) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
2) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).
3) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
4) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.

1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
2) In rabbits, isoproterenol and aminophylline significantly reduced the increased pulmonary artery pressure, vascular permeability, and fluid-flux associated with hydrochloric acid lung injury (Mizus et al, 1985).

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

1) Alkalinization of the urine may help prevent deposition of red cell breakdown products in renal tubular cells if hemolysis is occurring.
2) SODIUM BICARBONATE/INITIAL DOSE
3) SODIUM BICARBONATE/REPEAT DOSES
4) CAUTION

1) INDICATIONS
2) MOBILIZATION TEST

1) EFFICACY - Dimercaprol (BAL) is an effective arsenic chelator, but has the disadvantages of requiring painful intramuscular injections and having numerous side effects. BAL has been reported to result in clinical improvement and decrease in hospital days in children poisoned with arsenic (Woody & Kometani, 1948).
2) ADVERSE EFFECTS - Typical side effects which are dose related include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, convulsions, "leukotoxic effect," and reducing substances in the urine (Woody & Kometani, 1948).
3) DOSE - Usual dosage range is 3 to 5 milligrams/kilogram intramuscularly every 4 to 12 hours until symptoms resolve or another chelator is substituted. The dose used is dependent on the severity of symptoms and urinary arsenic levels.

1) EFFICACY - D-penicillamine has been successfully used in acute arsenic poisoning in children (Peterson & Rumack, 1977) Kuravilla et al, 1975; (Watson et al, 1981). It has the advantage of being an oral agent, but the disadvantages of not being able to be given to patients allergic to penicillin, not being retained well if patients are vomiting, and the theoretical problem of enhancing absorption of the arsenic-chelator complex. It does not appear to result in depletion of zinc and copper when given for several weeks (Peterson & Rumack, 1977).
2) ADVERSE EFFECTS - Long term therapy for the treatment of arthritis or Wilson's disease has resulted in fever, pruritus, leukopenia, thrombocytopenia, eosinophilia, and renal toxicity; these effects have not been reported when the drug is used for short-term heavy metal chelation (Gilman et al, 1985).
3) DOSE - The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day (Peterson & Rumack, 1977), but larger doses (i.e., up to 2 grams/day) may be required in adults.
4) In an experimental animal model, d-penicillamine was found to lack effectiveness in trivalent arsenic-poisoned mice and guinea pigs (Kreppel et al, 1989).

1) EFFICACY - 2,3-Dimercaptosuccinic acid (DMSA) is an investigational drug which appears to be a very effective arsenic chelator in experimental animals (Graziano et al, 1978) and man (Lenz et al, 1981; Kosnett & Becker, 1987; Fournier et al, 1988). In a patient treated with DMSA (30 milligrams/kilogram/day for 5 days) for long-term ingestion of arsenic, plasma concentrations were unchanged after treatment and renal arsenic excretion increased 1.5 fold (Fournier et al, 1988). DMSA has the advantage of being an oral agent as well as being relatively non-toxic.
2) In a double-blind, randomized crossover, placebo controlled study of patients with chronic environmental arsenical disease in West Bengal, patients were given placebo or DMSA 1400 mg/day for one week followed by 1050 mg/day for two additional weeks. The alternative treatment was then administered following a three week delay. Although both groups reported clinical improvement, treatment was no better than control (Guha Mazumder et al, 1998).

1) EFFICACY - N-acetylcysteine (NAC) has been shown to increase the LD50 of sodium arsenite in mice (Shum et al, 1981). NAC has the advantage of being both an oral and an intravenous agent, but has not been studied for this indication in humans and cannot presently be recommended for the treatment of arsenic poisoning.
2) THERAPEUTIC END-POINT - Repeat five-day courses of chelation therapy should be prescribed in severe poisonings until the 24-hour urine arsenic level falls below 50 micrograms/liter (Goldfrank et al, 1986; AMA, 1986).

1) Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy in some cases (Jenkins, 1966). However, once neuropathy has developed (usually 1 to 3 weeks after acute exposure), chelation with BAL may not be effective in reversing it (Heyman et al, 1956; Donofrio et al, 1987; Le Quesne & McLeod, 1977).
2) Physical therapy may be helpful for patients with established arsenical neuropathies.

1) Should be performed in the presence of any degree of renal failure, as the main route of excretion will be inhibited if this occurs. As the serum creatinine falls, urinary arsenic may increase (Giberson et al, 1976). Dialysanse of arsenic in two patients was 76 and 87 milliliters/minute (Vaziri et al, 1980). This may be greater than renal clearance in the presence of oliguria or renal failure.
2) Hemodialysis was instituted 4-hours postadmission in a 30-year-old male who ingested 6 ounces of a rodenticide containing 1.5 percent arsenous oxide (equivalent to 2,150 milligrams metallic arsenic), although the patient exhibited no evidence of renal impairment (Fesmire et al, 1988). Additional studies are needed to evaluate this regimen for safety and efficacy before it can be routinely recommended (Fesmire et al, 1988).

1) SUMMARY
2) DOPAMINE
3) NOREPINEPHRINE

1) SYSTEMIC TOXICITY - No cases of systemic arsenic poisoning following only eye exposure have been reported.
2) CONSULTATION - If significant eye irritation is present, prolonged initial flushing and early ophthalmologic consultation are advisable.

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

1) APPLICATION
2) DEBRIDEMENT
3) TREATMENT
4) TETANUS PROPHYLAXIS

1) Systemic arsenic poisoning can occur following dermal exposure to arsenic trichloride (Delepine, 1923; HSDB , 1991).

1) Alkalinization of the urine may help prevent deposition of red cell breakdown products in renal tubular cells if hemolysis is occurring.
2) SODIUM BICARBONATE/INITIAL DOSE
3) SODIUM BICARBONATE/REPEAT DOSES
4) CAUTION

1) INDICATIONS
2) MOBILIZATION TEST

1) EFFICACY - Dimercaprol (BAL) is an effective arsenic chelator, but has the disadvantages of requiring painful intramuscular injections and having numerous side effects. BAL has been reported to result in clinical improvement and decrease in hospital days in children poisoned with arsenic (Woody & Kometani, 1948).
2) ADVERSE EFFECTS - Typical side effects which are dose related include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, convulsions, "leukotoxic effect," and reducing substances in the urine (Woody & Kometani, 1948).
3) DOSE - Usual dosage range is 3 to 5 milligrams/kilogram intramuscularly every 4 to 12 hours until symptoms resolve or another chelator is substituted. The dose used is dependent on the severity of symptoms and urinary arsenic levels.

1) EFFICACY - D-penicillamine has been successfully used in acute arsenic poisoning in children (Peterson & Rumack, 1977) Kuravilla et al, 1975; (Watson et al, 1981). It has the advantage of being an oral agent, but the disadvantages of not being able to be given to patients allergic to penicillin, not being retained well if patients are vomiting, and the theoretical problem of enhancing absorption of the arsenic-chelator complex. It does not appear to result in depletion of zinc and copper when given for several weeks (Peterson & Rumack, 1977).
2) ADVERSE EFFECTS - Long term therapy for the treatment of arthritis or Wilson's disease has resulted in fever, pruritus, leukopenia, thrombocytopenia, eosinophilia, and renal toxicity; these effects have not been reported when the drug is used for short-term heavy metal chelation (Gilman et al, 1985).
3) DOSE - The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day (Peterson & Rumack, 1977), but larger doses (ie, up to 2 grams/day) may be required in adults.
4) In an experimental animal model, d-penicillamine was found to lack effectiveness in trivalent arsenic-poisoned mice and guinea pigs (Kreppel et al, 1989).

1) EFFICACY - 2,3-Dimercaptosuccinic acid (DMSA) is an investigational drug which appears to be a very effective arsenic chelator in experimental animals (Graziano et al, 1978) and man (Lenz et al, 1981; Kosnett & Becker, 1987; Fournier et al, 1988). In a patient treated with DMSA (30 milligrams/kilogram/day for 5 days) for long-term ingestion of arsenic, plasma concentrations were unchanged after treatment and renal arsenic excretion increased 1.5 fold (Fournier et al, 1988). DMSA has the advantage of being an oral agent as well as being relatively nontoxic.
2) In a double-blind, randomized crossover, placebo controlled study of patients with chronic environmental arsenical disease in West Bengal, patients were given placebo or DMSA 1400 mg/day for one week followed by 1050 mg/day for two additional weeks. The alternative treatment was then administered following a three week delay. Although both groups reported clinical improvement, treatment was no better than control (Guha Mazumder et al, 1998).

1) EFFICACY - N-acetylcysteine (NAC) has been shown to increase the LD50 of sodium arsenite in mice (Shum et al, 1981). NAC has the advantage of being both an oral and an intravenous agent, but has not been studied for this indication in humans and cannot presently be recommended for the treatment of arsenic poisoning.

1) Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy in some cases (Jenkins, 1966). However, once neuropathy has developed (usually 1 to 3 weeks after acute exposure), chelation with BAL may not be effective in reversing it (Heyman et al, 1956; Donofrio et al, 1987; Le Quesne & McLeod, 1977).
2) Physical therapy may be helpful for patients with established arsenical neuropathies.

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

1) Should be performed in the presence of any degree of renal failure, as the main route of excretion will be inhibited if this occurs. As the serum creatinine falls, urinary arsenic may increase (Giberson et al, 1976). Dialysanse of arsenic in two patients was 76 and 87 milliliters/minute (Vaziri et al, 1980). This may be greater than renal clearance in the presence of oliguria or renal failure.
2) Hemodialysis was instituted 4-hours postadmission in a 30-year-old man who ingested 6 ounces of a rodenticide containing 1.5 percent arsenous oxide (equivalent to 2,150 milligrams metallic arsenic), although the patient exhibited no evidence of renal impairment (Fesmire et al, 1988). Additional studies are needed to evaluate this regimen for safety and efficacy before it can be routinely recommended (Fesmire et al, 1988).

1) SKIN ULCERATION - Workers with significant arsenical dermatitis, ulcerations, or dermatoses may be overexposed and may need to be precluded from further exposure.

1) SUMMARY
2) DOPAMINE
3) NOREPINEPHRINE

a) Instantaneous hemodialysis clearance was 85 +/- 75 milliliters/minute without previous BAL and 87.5 +/- 75 milliliters/minute with a previous 250 milligram BAL injection.
b) BAL 250 milligrams was given one time only at approximately 20 hours postingestion.
c) One month after discharge the patient was admitted to another hospital for a sensory and motor polyneuritis involving both upper and lower limbs. Arsenic concentrations in blood and urine were not detectable, however, BAL was administered for 8 days at this institution. All neurologic signs resolved over 3 months.

a) Hemodialysis was instituted 4 hours postadmission in a 30-year-old male who ingested 6 ounces of a rodenticide containing arsenous oxide 1.5 percent (approximately 2,150 milligrams of metallic arsenic) although the patient exhibited no evidence of renal impairment (Fesmire et al, 1988).

a) As little as 20 milligrams of arsenic may produce life-threatening toxicity (Zaloga et al, 1970; Schoolmeester & White, 1980).
b) An oral dose of 120 mg of arsenic trioxide may be fatal (Finkel, 1983).

a) Two hundred milligrams of arsenic trioxide ingestion by an adult may be lethal (Baselt & Cravey, 1989; Baselt, 1988).
b) Acute ingestion of 9 to 14 milligrams of arsenic trioxide by a 16-month-old child produced classic gastrointestinal signs and symptoms of arsenic poisoning (Watson et al, 1981).
c) A 30-year-old man survived an ingestion of 6 ounces of "Blue Ball Rat Killer" containing 1.5% arsenous oxide (2,150 milligrams metallic arsenic per 6 ounces) with aggressive therapy (fluid resuscitation, chelation and hemodialysis) (Fesmire et al, 1988).

a) Significant toxicity may occur with large amounts of pentavalent salts in humans.
b) Pentavalent arsenic may be converted in vitro to trivalent arsenic.

1) LD50- (ORAL)RAT:
2) LD50- (SKIN)RAT: