1) Direct contact may produce conjunctival irritation or a characteristic dermatitis. Other skin findings may be melanosis, hyperkeratosis and hyperhidrosis. Hair loss and trophic nail changes may also occur with chronic exposure.

1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.

1) Maintain high urine output.

1) May prevent the deposition of 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) BAL - Symptomatic patients should be treated with BAL 3 to 5 mg/kg/dose IM every 4 to 12 hours. The dose and frequency depend on the degree of toxicity seen. Higher doses of BAL invariably cause adverse effects.
2) PENICILLAMINE - As symptoms and signs subside, change to oral D-penicillamine 100 mg/kg/day up to 2 g daily in four divided doses. If allergic to penicillamine, administer BAL for 5 days with tapering of the dose. In severely ill patients, combined therapy with both BAL and D-penicillamine should be considered.
3) ENDPOINT - Chelation therapy should be stopped when the urinary arsenic level falls below 50 mcg per 24 hours. If renal failure exists, dose of either chelator should be adjusted downward after loading dose.
4) DMSA - Dimercaptosuccinic acid (DMSA) is a chelator currently approved for the treatment of pediatric lead poisoning in the United States. It may be more effective and cause fewer side effects than BAL.

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 include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, convulsions, "leukotoxic effect," and reducing substances in the urine. Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy in some cases.
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) 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) Alkalinization of the urine may prevent deposition of red cell breakdown products from hemolysis in renal tubular cells.
3) 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.
4) 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.
5) Physical therapy may be helpful for patients with established arsenical neuropathies.
6) 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.
7) HEMODIALYSIS - should be performed in the presence of any degree of renal failure.
8) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
9) Restriction from further exposure may be necessary for workers with significant arsenical dermatitis, ulcerations, or dermatoses.
10) 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) Conjunctivitis, photophobia, dimness of vision, diplopia, and lacrimation may occur with chronic arsenic exposure (Heyman et al, 1956; Grant, 1993).

1) Symptoms and signs in the affected workers included paracentral scotomas, night blindness, photophobia, and visual impairment. The contribution of the Paris Green exposure to these findings is unclear.

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) ARSENIC SKIN LESIONS - 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).

1) 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).
2) These dysrhythmias may be secondary to electrolyte imbalances rather than a direct toxic effect of arsenic on the myocardium (Sittig, 1991).

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).
2) These ECG changes may be secondary to electrolyte imbalances rather than a direct toxic effect of arsenic on the myocardium (Sittig, 1991), although a direct, reversible effect on the myocardium has been postulated from animal experiments (Massmann & Opitz, 1954).

1) Upper respiratory tract irritation may result from inhalation exposure to Paris Green (EPA, 1985; Grant, 1993; OHM/TADS , 2000).

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

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

1) Toxic delirium and encephalopathy are complications of acute arsenic poisoning (Jenkins, 1966).
2) The encephalopathy may be permanent and result in cortical atrophy one to six months after exposure. Early institution of chelation therapy may not be successful in preventing arsenic encephalopathy (Fincher & Koerker, 1987).

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. It has been claimed that if BAL is administered within hours of ingestion, however, that neuropathy may be prevented (Jenkins, 1966), although this may not always be true (Marcus, 1987).

1) Seizures may occur (Hathaway et al, 1996; Harbison, 1998).

1) Arsenic is NOT likely to be a significant risk to human reproduction at permissible occupational exposure limits (Council on Scientific Affairs, 1985).
2) 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).

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) Arsenic compounds have typically induced birth defects in experimental animals at high doses which may have also been maternally toxic (OTA, 1985). High doses of inorganic arsenic administered to pregnant animals results in fetal resorptions; surviving offspring have defects of the genitourinary tract (Hayes & Lawes 1991).
3) 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) Arsenic is transferred across the placenta (Barlow & Sullivan, 1982). In studies of a population in Argentina exposed to environmental aresenic (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, compared with 70 percent in the urine of non-pregnant women, indicating that the methylation of arsenic may be upregulated during pregnancy (Concha et al, 1998).
2) 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; Nordstrom, 1979). The significance of this study to pure chronic arsenic exposure during pregnancy is unclear. Increased numbers of miscarriages were reported in Finland with mixed exposures which included arsenic compounds (Hemminki, 1980).

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.

1) AMA COUNCIL ON SCIENTIFIC AFFAIRS - Although arsenic compounds are likely fetotoxic in humans, exposure at permissible occupational levels is not likely to present a significant risk to human reproduction (Council on Scientific Affairs, 1985).

1) Six women developing arsenical encephalopathy during the fourth to eighth month of pregnancy delivered normal children (Schardein, 1993).

1) Arsenic is excreted in the breast milk in both experimental animals and humans. There may be some risk to nursing infants of mothers exposed to arsenic, based on studies of Japanese children who drank arsenic-contaminated powdered milk and who may have suffered problems in later brain development (Barlow & Sullivan, 1982).

1) Not Listed

1) The potential carcinogenicity of arsenic compounds has been reviewed (Berlin et al, 1991). The Occupational Safety and Health Administration (OSHA) has linked arsenic to cancer of the skin, lungs, lymph glands, and bone marrow (Anon, 1979; IARC, 1973), and possibly angiosarcoma of the liver and stomach cancer (ILO, 1983).
2) Typically, there is a 15 to 30 year latent period before developement of cancer (ILO, 1983). The evidence for human arsenical carcinogenicity is much stronger than carcinogenicity evidence in experimental animals (a somewhat unique circumstance). It has not been carcinogenic in experimental animals, except when implanted (RTECS , 1993).
3) The US Environmental Protection Agency has classified inorganic arsenical compounds as Class A carcinogens, based on sufficient human epidemiological evidence (EPA, 1988).
4) Exposure to as little as 1 gram of arsenic per year has been associated with CANCER (HSDB , 1993). Paris Green has been implicated as a human carcinogen. 0ne case of multiple keratoses and chronic lymphatic leukemia with a 30-year latent period has been described in a worker with a history of one-year occupational dermal exposure to Paris Green in a pesticide manufacturing facility (Leyh & Rothlaender, 1985).
5) Arsenic is an INDIRECT CARCINOGEN. It causes cancer by a mechanism of generalized gene induction (Appel et al, 1984), rather than inducing mutations in specific genes. The question of whether or not there is a threshold dose for cancer induction by arsenic has been a matter of much debate. A literature review concluded that the threshold dose for arsenic-induced cancer is the same as that for arsenical skin disease: 400 mcg per day. Dermal hyperpigmentation may be a sensitive indicator of risk for subsequent development of cancer (Stohrer, 1991).
6) 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) 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).
7) Arsenic exposure has been associated with skin cancers, and possibly with bronchogenic cancer (Wagner et al, 1979) ACGIH, 1986; (IARC, 1973; HSDB , 1993). 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 bladder, kidney, skin, prostate, lung, and liver cancer (Chen et al, 1988).
8) One worker who was exposed to arsenious oxide and sodium arsenite for 20 years developed cirrhosis of the liver and primary liver carcinoma (Harbison, 1998).
9) One case of multiple keratoses and chronic lymphatic leukemia with a 30-year latency period has been described in a worker with a history of one-year occupational dermal exposure to Paris Green in a pesticide manufacturing facility (Leyh & Rothlaender, 1985).
10) In additional environmental studies in various regions where arsenic exposure is endemic, recent epidemiological 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).

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

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) Monitor serum electrolytes in patients with significant vomiting, diarrhea, or hypotension from fluid "third spacing."
3) This agent may cause nephrotoxicity. Monitor renal function tests and urinalysis in patients with significant exposure.
4) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.

1) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.

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).

1) HAIR

1) Aggressive decontamination with gastric lavage is recommended. If X-ray demonstrates arsenic in the lower GI tract, whole bowel irrigation should be considered. Activated charcoal may not bind significant amounts, but is recommended until definitive quantitative data are available. Fluid repletion should begin as soon as possible.
2) 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).
3) PRECAUTIONS:
4) LAVAGE FLUID:
5) COMPLICATIONS:
6) CONTRAINDICATIONS:

1) Preliminary results suggest that activated charcoal may not be of therapeutic value in the treatment of acute arsenic poisoning (pp 5-1990).
2) CHARCOAL ADMINISTRATION
3) CHARCOAL DOSE

1) Whole bowel irrigation with polyethylene glycol electrolyte lavage solution may be a relatively safe and effective means of rapid gastrointestinal decontamination (Lee et al, 1995).

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 tachycardia or ventricular fibrillation may occur after acute arsenic poisoning and should be treated with DC countershock and standard antiarrhythmic agents.
2) VENTRICULAR DYSRHYTHMIAS SUMMARY
3) LIDOCAINE
4) PROCAINAMIDE

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 END-POINT
3) MOBILIZATION TEST

1) 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 the patient's symptoms and the urinary arsenic levels.
2) ADVERSE EFFECTS: Typical side effects which are dose related include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, seizures, "leukotoxic effect", and reducing substances in the urine (Woody & Kometani, 1948).
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) SUMMARY
2) DIAZEPAM
3) NO INTRAVENOUS ACCESS
4) LORAZEPAM
5) PHENOBARBITAL
6) OTHER AGENTS

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 arsenic disease in West Bengal, patients were given placebo or DMSA 1,400 mg/day for one week, followed by 1,050 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) 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) 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 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) CONSULTATION - If significant eye irritation is present, prolonged initial flushing and early ophthalmologic consultation are advisable. Of note, no cases of systemic arsenic poisoning have been reported following only eye exposure.

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) 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) The urine arsenic level which should prompt chelation in an asymptomatic patient has been said to be 200 micrograms/liter (Kersjes et al, 1987).
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 arsenic disease in West Bengal, patients were given placebo or DMSA 1,400 mg/day for one week, followed by 1,050 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) 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) 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) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
2) Workers with significant arsenical dermatitis, ulcerations, or dermatoses 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) Acute ingestion of 9 to 14 milligrams of arsenic trioxide by a 16-month-old child produced classic GI signs and symptoms of arsenic poisoning (Watson et al, 1981).

a) 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) OCCUPATIONAL EXPOSURES (ACGIH, 1986) -

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