Arsine is a colorless hydride gas (AsH₃) formed when arsenic comes in contact with hydrogen or with reducing agents in aqueous solution. Typically, exposure to arsine gas occurs in smelting operations or other industrial settings when arsenic-containing ores, alloys, or metallic objects come in contact with acidic (or occasionally alkaline) solutions and newly formed arsine is liberated. Arsine is also used as a dopant in the microelectronics industry, and it may be accidentally encountered in the recycling of scrap gallium arsenic semiconductors.

Arsine is a potent hemolytic agent. Recent investigations suggest that hemolysis occurs when arsine interacts with oxyheme in hemoglobin to form a reactive intermediate that alters transmembrane ion flux and greatly increases intracellular calcium. Note: Arsenite and other oxidized forms of arsenic do not cause hemolysis. Deposition of massive amounts of hemoglobin in the renal tubule can cause acute renal injury. Massive hemolysis also decreases systemic oxygen delivery and creates hypoxic stress, and arsine and/or its reaction products exert direct cytotoxic effects on multiple organs.

Arsine is the most toxic form of arsenic. Acute exposure guideline levels (AEGLs) recently developed by the US Environmental Protection Agency and the National Research Council indicate that disabling effects (AEGL-2) may occur after 30 minutes of exposure to ≥0.21 ppm, 1 hour of exposure to ≥0.17 ppm, or 8 hours of exposure to ≥0.02 ppm. Lethal or life-threatening effects (AEGL-3) may occur from 30 minutes of exposure to ≥0.63 ppm, 4 hours of exposure to ≥0.13 ppm, or 8 hours of exposure to ≥0.06 ppm. The level considered by the National Institute for Occupational Safety and Health (NIOSH; 1994) as “immediately dangerous to life or health” (IDLH) is 3 ppm. The odor threshold of 0.5-1.0 ppm provides insufficient warning properties. Exclusive dermal exposure did not result in absorption in a hairless mouse model, suggesting that percutaneous absorption will not pose a risk to first responders or workers with adequate respiratory protection.

1. Acute effects. Because arsine gas is not acutely irritating, inhalation causes no immediate symptoms. Those exposed to high concentrations may sometimes detect a garlic-like odor, but more typically they are unaware of the presence of a significant exposure. In most industrial accidents involving arsine, the hazardous exposure occurred over the course of 30 minutes to a few hours.
2. After a latent period of 2-24 hours (depending on the intensity of exposure), massive hemolysis occurs, along with early symptoms that may include malaise, headache, fever or chills, and numbness or coldness in the extremities. There may be concomitant GI complaints of nausea, vomiting, and cramping pain in the abdomen, flank, or low back. In severe exposures, abrupt cardiovascular collapse and death may occur within 1 or 2 hours.
3. Hemoglobinuria imparts a dark, reddish color to the urine, and the skin may develop a copper, bronze, or “jaundiced” discoloration that may be attributable to elevated plasma hemoglobin.
4. Oliguria and acute renal failure often occur 1-3 days after exposure and are a major aspect of arsine-related morbidity.
5. A minority of patients may develop agitation and delirium within 1-2 days of presentation.
6. Chronic arsine poisoning, a rarely reported condition, has been associated with headache, weakness, shortness of breath, nausea, vomiting, and anemia.

Arsine poisoning should be suspected in a patient who presents with the abrupt onset of hemolysis, hemoglobinuria, and progressive oliguria. A consistent work history or another likely source of exposure increases the index of suspicion but is not always apparent.

1. Specific levels. Urine and whole-blood arsenic levels may be elevated but are rarely available in time to assist with prompt diagnosis and management. Whole-blood arsenic concentrations in patients with severe arsine poisoning have ranged from several hundred to several thousand micrograms per liter.
2. Other useful laboratory studies
   1. The CBC in the first few hours after acute exposure may be normal or reveal only moderate depression of the hematocrit or hemoglobin. However, within approximately 12-36 hours these values will decline progressively, with hemoglobin levels declining to 5-10 g/dL. The peripheral blood smear may reveal erythrocyte fragmentation and abnormal red blood cell forms, including characteristic “ghost cells” in which an enlarged membrane encloses a pale or vacant interior. Leukocytosis is common. Measurement of plasma or serum hemoglobin may guide management (see below).
   2. Initial urinalysis will typically be heme-positive on dipstick, but with scant formed red blood cells on microscopic examination. Later, as oliguria progresses, an active urine sediment with red blood cells and casts will often emerge. Quantitative measurement of urine hemoglobin may rise to 3 g/L during significant hemolysis and in some instances may exceed 10 g/L.
   3. Serum bilirubin may show mild-to-moderate elevations (eg, 2-5 mg/dL) during the first 48 hours, with only a slight rise in liver aminotransferases.
   4. Increases in BUN and serum creatinine will reflect acute renal insufficiency.

1. Emergency and supportive measures
   1. Provide vigorous IV hydration and, if needed, osmotic diuresis with mannitol to maintain urine output and reduce the risk for acute hemoglobinuric renal failure.
   2. Clinical reports indicate that prompt exchange transfusion with whole blood is a key therapeutic intervention and should be initiated for patients with a free serum hemoglobin level of 1.5 g/dL or higher and/or signs of renal insufficiency or early acute tubular necrosis. Because of the time delay needed to obtain matched blood, the possible need for exchange transfusion in significantly exposed patients should be anticipated soon after they present.
   3. Hemodialysis may be needed to treat progressive renal failure but is not a substitute for exchange transfusion, which, unlike hemodialysis, removes arsenic-hemoprotein complexes thought to contribute to the ongoing hemolytic state.
2. Specific drugs and antidotes
   1. The scant clinical experience with chelation in acute arsine poisoning is inconclusive, but limited animal and in vitro experimental studies suggest it is reasonable to initiate treatment with dimercaprol (BAL), a relatively lipid-soluble chelator, in patients who present within 24 hours of exposure. The dose of dimercaprol during the first 24 hours is 3-5 mg/kg every 4-6 hours by deep IM injection.
   2. After 24 hours, consider chelation with the water-soluble dimercapto chelating agents: oral or parenteral unithiol (DMPS) or oral succimer (DMSA).
   3. Note that the recommendation to use dimercaprol rather than unithiol or succimer during the initial phases of poisoning is unique to arsine and differs from the chelation recommendation for poisoning by other inorganic arsenicals, in which initial use of unithiol is favored.
   4. Chelation is of uncertain efficacy and should not substitute for or delay the vigorous supportive measures outlined earlier.
3. Decontamination. Remove the victim from exposure. First responders should use self-contained breathing apparatus or air-supplied respirators to protect themselves from any arsine remaining in the environment.
4. Enhanced elimination. As noted earlier, prompt exchange transfusion with whole blood is useful in patients with evidence of significant active hemolysis or evolving renal insufficiency. Whole donor blood may be infused through a central line at the same rate of blood removal through a peripheral vein, or techniques using automated cell separators to exchange both erythrocytes and plasma can be considered.