Arsine gas exposure

Background

  • Arsine gas (AsH₃) is the most acutely toxic form of arsenic.
  • It is a colorless, nonirritating gas that causes massive intravascular hemolysis leading to acute renal failure and death.
  • Arsine poisoning is distinct from inorganic arsenic poisoning — it does not produce classic arsenicosis, and chelation therapy is not effective.[1]
  • Arsine (AsH₃) is a colorless, heavier-than-air gas with a mild garlic-like or fishy odor (odor threshold ~0.5 ppm)
  • Warning properties are inadequate — toxic effects occur at or below the concentration at which odor is detectable[1]
  • Arsine is extremely flammable and decomposes above 230°C (446°F)
  • Sources of exposure:
    • Occupational (most common): semiconductor/microchip manufacturing (gallium arsenide wafer production), metal smelting and refining, lead/zinc/copper ore processing, battery manufacturing, soldering, galvanizing
    • Generated when arsenic-containing metals contact acid or water/moisture — may be produced unexpectedly during industrial processes[2]
    • Cleaning of tanks, drums, or pipes that contained arsenic-bearing materials
  • Extremely toxic:[3]
    • 150-250 ppm: immediately fatal
    • 25-50 ppm for 30 minutes: massive hemolysis, potentially fatal
    • 10 ppm: delirium
    • 3 ppm for several hours: symptomatic
    • 0.15 ppm: may produce mild symptoms
  • Prior to the advent of hemodialysis, arsine-induced renal failure was 100% fatal[3]
  • Current mortality rate approximately 25% with modern ICU care

Mechanism of toxicity

  • Arsine is rapidly absorbed through the lungs and binds to hemoglobin in red blood cells
  • Causes rapid, massive intravascular hemolysis through oxidative damage to RBC membranes[2]
    • Arsine depletes reduced glutathione in erythrocytes
    • Generates reactive oxygen species → lipid peroxidation of RBC membranes → membrane rupture
    • Persons with G6PD deficiency are more susceptible to hemolysis[4]
  • Free hemoglobin released from hemolyzed RBCs → precipitates in renal tubules → acute tubular necrosis (ATN) and oliguric renal failure
  • Arsine may also exert direct nephrotoxicity by inhibiting renal tubular cell respiration, independent of hemoglobin deposition[5]
  • Arsine does NOT produce classic arsenic intoxication — the pathophysiology is fundamentally different[1]

Healthcare worker safety

  • Small amounts of arsine may be trapped in victim's clothing/hair after massive exposure, but quantities are unlikely to create significant hazard for hospital personnel away from the scene[1]
  • Patients exposed only to arsine gas do not require decontamination
  • Use standard precautions; chemical-protective clothing generally not required for gas exposure
  • SCBA required for responders at the scene

Clinical features

  • Patients may appear initially well — symptoms may be delayed 2-24 hours after exposure[1]
  • The classic triad is: garlic/fishy odor + dark red/brown urine (hemoglobinuria) + jaundice

Early symptoms (30 minutes - several hours)

  • Malaise, fatigue, headache
  • Nausea, vomiting, crampy abdominal pain (among the earliest signs)
  • Thirst, shivering
  • Dyspnea
  • Garlic-like or fishy odor on breath (may not be detectable)

Hemolytic phase (hours to 24 hours)

  • "Blackwater" urine — dark red, brown, or port wine–colored urine from hemoglobinuria (classic finding)[3]
  • Jaundice (from hemolysis; may develop within 24-48 hours)
  • Rapidly progressive anemia (hemoglobin may drop below 10 g/dL)
  • Tachycardia
  • Pallor progressing to bronze-yellow skin discoloration (jaundice + anemia)
  • Hemolysis may continue for up to 96 hours after exposure[4]

Renal phase (24-72+ hours)

  • Oliguria/anuria — acute renal failure may not be evident until up to 72 hours after exposure[1]
  • Flank pain (renal capsular distension)
  • Fluid overload, pulmonary edema
  • Uremia

Cardiac

  • Hyperkalemia (from massive hemolysis + renal failure) → peaked T waves, conduction blocks, cardiac arrest[5]
  • ECG: high-peaked T waves, nonspecific ST-T changes, various degrees of heart block
  • Direct myocardial toxicity may also contribute

Neurologic (delayed, weeks to months)

  • Peripheral neuropathy — may develop 1-6 months after acute exposure (similar to inorganic arsenic)[1]
  • Encephalopathy, cognitive changes, psychiatric disturbances

Differential diagnosis

Intravascular hemolysis (other causes)

Other toxic gas exposures

Other causes of dark/bloody urine


Toxic gas exposure

Microangiopathic Hemolytic Anemia (MAHA)

Evaluation

Workup

  • CBC with peripheral smear:[5]
    • Anemia (may be severe; hemoglobin <10 g/dL)
    • Reticulocytosis, leukocytosis
    • Peripheral smear: RBC fragments, ghost cells, anisocytosis, poikilocytosis, basophilic stippling
    • Blue-green cast to WBC nuclei on unstained preparations (reported but uncommon)
  • Hemolysis markers:
    • Plasma free hemoglobin — elevated
    • Haptoglobin — decreased or undetectable
    • LDH — markedly elevated
    • Indirect bilirubin — elevated
    • Direct Coombs test — NEGATIVE (critical: this is Coombs-negative hemolytic anemia; distinguishes from immune-mediated hemolysis)[5]
  • Urinalysis:
    • Hemoglobinuria — urine dipstick positive for blood, but no RBCs on microscopy
    • Tubular casts
  • BMP: renal function (BUN, creatinine), potassium (expect hyperkalemia)
  • Hepatic function panel: may show elevated transaminases, bilirubin
  • ECG: monitor for hyperkalemia-related changes (peaked T waves, widened QRS, heart block)
  • Chest radiograph: pulmonary edema if fluid overloaded
  • Urinary arsenic: may be elevated for weeks after exposure; provides index of exposure extent but does not guide acute management[1]
  • Blood arsenic: may be elevated acutely (<2 days post-exposure); clears rapidly from blood
  • Type and screen — anticipate need for transfusion or exchange transfusion
  • Serum electrolytes, calcium — monitor frequently

Diagnosis

  • Clinical: occupational exposure + garlic odor + dark urine + Coombs-negative hemolytic anemia + renal failure
  • Even if arsine odor was not detected at the scene, exposure may still be significant[1]
  • High index of suspicion in any industrial worker with unexplained hemolysis

Management

There is no specific antidote for arsine poisoning. Treatment is supportive care focused on protecting renal function and managing hemolysis.[1]

Resuscitation

  • Airway, breathing, circulation per standard protocols
  • Supplemental oxygen
  • IV access; continuous cardiac monitoring

Decontamination

  • Patients exposed only to arsine gas do not require decontamination[1]
  • Remove contaminated clothing only if liquid arsine (compressed gas) exposure or co-exposure to arsenic-containing materials
  • Irrigate eyes with water if exposed to liquid

Renal protection (critical)

  • Aggressive IV fluid resuscitation to maintain high urine output (target 2-3 mL/kg/hr)[1]
  • Urinary alkalinization: add 50-100 mEq NaHCO₃ to 1 L of D5W 0.25 NS; infuse to maintain urine pH >7.5 until urine is hemoglobin-free
    • Rationale: alkaline urine reduces hemoglobin precipitation in renal tubules
    • Note: the role of alkalinization is somewhat controversial but widely recommended[5]
  • Low-dose dopamine may help preserve renal blood flow (limited evidence)
  • Hemodialysis if acute renal failure develops[1]
    • Does not effectively remove arsine-hemoglobin or arsine-haptoglobin complexes
    • Indicated for standard renal failure indications: uremia, hyperkalemia, volume overload, acidosis

Hemolysis management

  • Exchange transfusion: considered the most effective intervention for severe hemolysis[5]
    • Removes free hemoglobin, arsine-damaged RBCs, and hemoglobin-haptoglobin complexes from circulation
    • Reduces renal hemoglobin load
    • Should be considered early in patients with massive hemolysis
  • Packed RBC transfusion: for symptomatic anemia; adequate for mild hemolysis[5]
  • Monitor serial hemoglobin/hematocrit (hemolysis may progress for up to 96 hours)

Hyperkalemia

  • Aggressive management per standard protocols (calcium gluconate, insulin/dextrose, sodium bicarbonate, kayexalate, hemodialysis)
  • May be severe due to combined massive hemolysis + renal failure
  • Continuous cardiac monitoring

Chelation therapy

  • Chelation (BAL/dimercaprol) is NOT effective and NOT recommended for acute arsine poisoning[1][5]
    • BAL does not prevent or reduce hemolysis even when given soon after exposure
    • Chelation addresses inorganic arsenic toxicity, not arsine's hemolytic mechanism
    • Unlike inorganic arsenic poisoning, chelation should not be used routinely

Disposition

  • All symptomatic patients and all patients with significant exposure history: admit to ICU[5]
    • Continuous cardiac monitoring
    • Hourly urine output monitoring for at least 24 hours
    • Serial CBC, hemolysis markers, renal function, potassium every 4-6 hours initially
  • Asymptomatic patients with possible exposure: observe for minimum 24 hours with serial labs[1]
    • Onset of hemolysis may be delayed up to 24 hours
    • Acute renal failure may not be evident for up to 72 hours
  • Patients with no signs of hemolysis after 24 hours of observation: may discharge with close follow-up and return precautions[1]
  • Outpatient follow-up should include:
    • Serial renal function monitoring
    • Monitoring for delayed peripheral neuropathy (may appear 1-6 months post-exposure)
    • Neuropsychiatric evaluation for possible encephalopathy
  • Recovery from severe arsine poisoning may take weeks to months
  • Contact Poison control (1-800-222-1222 in the US) for all cases

See Also

External Links

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 Arsine Medical Management Guidelines. Agency for Toxic Substances and Disease Registry (ATSDR). CDC.
  2. ↑ 2.0 2.1 Fowler BA, Weissberg JB. Arsine poisoning. N Engl J Med. 1974;291(22):1171-1174. doi:10.1056/NEJM197411282912207
  3. ↑ 3.0 3.1 3.2 Arsine Poisoning Clinical Presentation. Medscape. 2024.
  4. ↑ 4.0 4.1 Region VII Disaster Health Response Ecosystem. Hazardous Materials Guideline: Arsine. 2024.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Pigott DC, Liebelt EL. Arsine. In: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose. 4th ed. 2007.
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