Toxicology – Arsine (AsH₃)

Core concept

Arsine is a potent inhaled hemolytic poison. It is a colorless, nonirritating, flammable gas that may have a garlic-like odor. Its major toxicity is rapid, severe intravascular hemolysis, which can lead to hemoglobin-induced acute kidney injury.

Exposure

Exposure is usually occupational or industrial, especially when arsenic-containing materials are exposed to strong acids or heat.

Common settings include:

• Smelting and refining of metals and ores
• Galvanizing
• Soldering
• Metal etching and plating
• Metallurgy
• Fossil-fuel combustion
• Semiconductor and microelectronics manufacturing

A major danger is that odor is unreliable, and toxic exposure may occur below the odor-detection threshold.

Mechanism

Arsine → enters RBCs → oxidative injury and glutathione depletion → severe Coombs-negative intravascular hemolysis

This may progress to:

Hemolysis → free hemoglobin → hemoglobinuria → renal tubular injury → acute kidney injury

Severe poisoning may cause multiorgan failure and death.

Toxicity

• Immediate death has been reported at approximately 150 ppm
• NIOSH IDLH: 3 ppm
• Occupational TWA historically cited: 0.05 ppm
• Clinical toxicity is often delayed by 2–24 hours

The delayed onset is an important diagnostic pitfall.

Clinical Features

Characteristic severe poisoning

A classic triad is:

Abdominal pain + dark/red urine + bronze skin discoloration

General symptoms

• Headache
• Weakness
• Chills
• Thirst
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain

Hematologic

• Severe intravascular hemolysis
• Falling hemoglobin and hematocrit
• Low haptoglobin
• Elevated markers of hemolysis
• Usually direct antiglobulin (Coombs) negative

Renal

Dark red urine commonly appears within approximately 4–12 hours and may represent:

• Hemoglobinuria
• Hematuria

Massive hemoglobinuria can cause acute tubular necrosis and acute renal failure.

Skin and eyes

Within approximately 12–36 hours:

• Dusky or bronze skin discoloration
• Reddish conjunctival discoloration

The bronze coloration is related predominantly to hemoglobin rather than bilirubin.

Cardiovascular

• Peaked T waves or other T-wave changes
• Ventricular dysrhythmias may occur
• Electrolyte disturbances associated with hemolysis and renal failure may worsen cardiac toxicity

Diagnosis

Diagnosis is based mainly on:

Exposure history + evidence of intravascular hemolysis

Essential investigations

Serial monitoring should include:

• Complete blood count
• Peripheral blood smear
• Serum haptoglobin
• Electrolytes
• BUN
• Creatinine
• Urinalysis
• ECG

Additional useful investigations include:

• LDH
• Indirect bilirubin
• Reticulocyte count
• Plasma-free hemoglobin

Blood and urine arsenic concentrations may help document exposure, but treatment should not be delayed while awaiting arsenic levels.

Treatment

1. Remove from exposure

Immediately remove the patient from the contaminated environment while ensuring appropriate protection for rescuers.

2. Oxygen

Administer supplemental oxygen. The cited source recommends 100% oxygen initially.

3. Treat hemolysis

• Monitor hemoglobin and hematocrit closely
• Provide packed red blood cell transfusion when clinically indicated
• Monitor for rapidly progressive hemolysis

4. Prevent and manage renal injury

• IV fluids when appropriate
• Maintain adequate urine output
• Monitor fluid balance carefully
• Serial potassium, electrolytes, and renal function
• Avoid additional nephrotoxins

The older source suggests maintaining urine output at approximately 1–2 mL/kg/hour, although fluid management should be individualized.

5. Hemodialysis

Hemodialysis may be necessary if acute kidney injury causes:

• Refractory hyperkalemia
• Severe metabolic acidosis
• Fluid overload
• Uremic complications

Dialysis treats the complications of renal failure rather than acting as a specific antidote to arsine.

6. Exchange transfusion

Exchange transfusion has historically been advocated in severe arsine poisoning, particularly when massive hemolysis is present.

This should be considered in consultation with toxicology, hematology, nephrology, and critical care specialists.

Antidote

There is no established specific antidote for arsine poisoning.

Dimercaprol (BAL) is not reliably effective and does not appear to prevent or reduce arsine-induced hemolysis.

This is an important distinction from some forms of inorganic arsenic poisoning, where chelation therapy may have a role.

Disposition

Patients with significant suspected arsine exposure generally require hospital admission and close monitoring, because symptoms and hemolysis may be delayed.

Severe or suspected clinically important poisoning warrants ICU-level care.

Patients should not be discharged prematurely because clinical deterioration may occur many hours after exposure.

Prognosis

Large exposures may cause:

• Rapid death
• Massive hemolysis
• Acute renal failure
• Multiorgan injury

Outcome depends largely on exposure severity and the development of hemolysis and renal complications.

High-Yield Toxicology Pearls

Arsine = hemolysis.

Think of arsine poisoning when there is:

Industrial exposure + delayed symptoms + Coombs-negative intravascular hemolysis + dark urine + acute kidney injury

Key points:

• Main route: inhalation
• Primary target: red blood cells
• Hallmark toxicity: massive intravascular hemolysis
• Classic urine finding: hemoglobinuria
• Major complication: acute kidney injury
• Symptoms may be delayed 2–24 hours
• No specific antidote
• BAL is not reliably useful
• Severe cases may require RBC transfusion, exchange transfusion, and hemodialysis