Irritants and asphyxiants

Exposure to chemical asphyxiants and/or irritants can occur in the household or workplace, in the context of war or terror attacks, or as a result of natural or man-made disasters. Irritants such as ammonia, chlorine, phosgene, and tear gas are chemical agents that cause irritation or an inflammatory skin and mucous membrane response. Exposure to irritants can lead to cough, eye irritation, mucous membrane and skin burns, acute lung injury, and chemical pneumonitis. Asphyxiants primarily cause systemic and tissue hypoxia by displacing oxygen from inhaled air (e.g., carbon dioxide, methane) or by disrupting oxygen transport and/or oxidative metabolism (e.g., carbon monoxide, phosphine, nitric oxide). Exposure to asphyxiants can lead to hypoxemia, metabolic acidosis, and cardiovascular collapse. Symptoms and signs of both irritant and asphyxiant poisoning may be seen following exposure to certain substances, such as hydrogen sulfide or nitrogen oxides. Management is based primarily on the clinical manifestations. The use of personal protective equipment (PPE) and thorough decontamination is essential to prevent further patient and medical staff exposure. Resuscitation and supportive care are the mainstays of treatment. In some cases, substance-specific measures (e.g., antidotes) are indicated.

This article outlines common sources of irritant and asphyxiant poisoning. Other hazardous chemicals are discussed in “Smoke inhalation injury,” “Organic solvent toxicity,” “Hydrocarbon toxicity,” “Carbon monoxide toxicity,” “Carbon dioxide poisoning,” “Cyanide toxicity,” “Caustic agents,” and “Cholinergic poisoning.”

• Irritant: a chemical agent that causes irritation or an inflammatory skin and mucous membrane response (e.g., ammonia, chlorine, phosgene)
  • Highly water-soluble irritants cause symptoms immediately upon exposure to mucous membranes (e.g., cough, tearing).
  • Poorly water-soluble irritants cause symptoms of delayed-onset lung injury (e.g., dyspnea, wheezing, chest tightness) within hours to days after exposure.
• Simple asphyxiant: a gas that displaces oxygen from inhaled air, causing hypoxemia (e.g., carbon dioxide, methane, nitrogen, helium)
• Chemical asphyxiant: a gas that causes tissue hypoxia by disrupting oxygen transport and/or oxidative metabolism (e.g., carbon monoxide, phosphine, nitric oxide)

Initial management ^[1][2]

• Don PPE.
• Follow the ABCDE approach for poisoning, especially:
  • Laryngoscopy if there are signs of oropharyngeal irritation, stridor, odynophagia, or dysphagia
    • Severe laryngeal or supralaryngeal irritation: Perform intubation.
    • Mild to moderate irritation: Reexamine in 30–90 minutes or if clinical status worsens.
  • Respiratory support (e.g., supplemental oxygen, noninvasive PPV) as needed
    • Administer an inhaled bronchodilator, e.g., albuterol (off-label) for bronchospasm.
    • Consider corticosteroids, e.g., prednisone (off-label) for exacerbations of underlying reactive airway disease. ^[1][2]
  • Body surface decontamination
• Consider substance-specific treatment.
• Begin treatment of ocular chemical burns.
• Initiate treatment of burns and consider transfer to a burn center.
• Call poison control: In the US, the national Poison Help line is 1-800-222-1222.

Diagnostics ^[1]

Asphyxiant and irritant poisoning is a clinical diagnosis; laboratory studies are used to assess for secondary complications, guide subsequent management, and, in specific cases, confirm the diagnosis.

• Obtain routine laboratory studies.
  • CBC
  • BMP
  • POC glucose
• Consider additional studies.
  • ABG
  • CXR
  • ECG
  • Substance-specific diagnostics
• Consider confirmatory studies for substance-specific exposures.

Consider ABG to assess for hypoxemia, as pulse oximetry may be inaccurate if methemoglobin or carbon monoxide is present. ^[1]

Disposition ^[1]

Disposition is based on the type of exposure and the severity of symptoms.

• Admit critically ill patients to the ICU.
• Admit for 24–48 hours of observation if any of the following are present:
  • High-risk exposure (e.g., prolonged or high-concentration exposure, exposure in an enclosed space)
  • Initial presentation with significant signs or symptoms (e.g., altered mental status or coma, chest pain, ECG changes)
  • Exposure with delayed effects (e.g., with phosgene)
  • Significant underlying medical conditions (e.g., asthma, COPD, heart disease)
• Discharge after 6 hours of observation is appropriate for patients with either of the following:
  • Exposure to intermediately or poorly water-soluble irritants (e.g., chlorine, nitrogen oxides)
  • No symptoms or minimal symptoms that are improving after initial mild asphyxia
• Discharge after clinical evaluation is appropriate for patients with both of the following:
  • Exposure to highly water-soluble irritants (e.g., ammonia, hydrogen sulfide, hydrogen fluoride)
  • No symptoms or minimal symptoms that are improving

Observe patients with signs of upper airway irritation in the emergency department or ICU until signs subside. Be prepared for difficult airway management. ^[1]

Provide discharged patients with return precautions for new or worsening symptoms. ^[1]

This section provides an overview of environmental ammonia exposure. See “Hyperammonemia” for endogenous causes.

• Characteristics ^[1][3]
  • Highly water-soluble irritant
  • Colorless
  • Pungent odor
• Sources of exposure ^[3]
  • Accidents during manufacturing or transportation
  • Use of cleaning products, fertilizers, or refrigerants that contain ammonia (e.g., anhydrous ammonia)
• Pathophysiology: exothermic reaction upon contact with moist surfaces (e.g., mucous membranes) → thermal and caustic injury to skin, eyes, oral cavity, and/or respiratory tract ^[3]
• Clinical features ^[3][4]
  • Respiratory tract: throat irritation, cough, dyspnea, rhinorrhea, chest tightness ^[3]
  • Ocular: conjunctival irritation, corneal damage
  • Dermal: pain, irritation, necrosis, blistering, deep burns, frostbite
  • Gastrointestinal : corrosive injury to mouth, throat, esophagus, and/or stomach
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific diagnostics ^[4]
  • CXR: may show pulmonary edema
  • No confirmatory study is available.
• Substance-specific management
  • For ingestional exposure: ^[4]
    • Avoid gastrointestinal decontamination.
    • Have the patient drink 4–8 oz of water.
    • Consider GI consult for EGD.
  • For severe inhalational injury: consider pulmonary consult for bronchoscopy.
  • No specific antidote is available.
• Complications ^[4]
  • Respiratory: chronic lung disease (e.g., asthma, pulmonary fibrosis), respiratory failure
  • Dermal: severe burns, deep ulcerations, chronic dermatitis
  • Ocular: cataracts, glaucoma, blindness
  • Gastrointestinal: GI perforation, strictures

Ammonia exposure typically manifests with the immediate onset of superficial mucosa symptoms (e.g., lacrimation, rhinorrhea, burning sensation). Severe exposure may lead to airway obstruction and pulmonary edema. ^[3]

• Characteristics ^[1][5]
  • Intermediately to poorly water-soluble irritant
  • Green-yellow
  • Pungent odor
• Sources of exposure ^[5]
  • Industrial: e.g., bleaching paper, textiles, paint
  • Household: e.g., cleaning products, pool disinfectant
• Pathophysiology: contact with moisture → formation of hypochlorous or hydrochloric acid and free oxygen radicals → irritation of the skin and mucous membranes (e.g., eyes, respiratory tract) ^[5]
• Clinical features ^[5]
  • Respiratory: upper airway irritation, cough, bronchospasm, dyspnea, acute lung injury, cyanosis, hemoptysis
  • Ocular: lacrimation, conjunctivitis
  • Dermal: burning pain, inflammation, blistering
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific diagnostics
  • Laboratory studies: hyperchloremic metabolic acidosis (in massive chlorine inhalation)
  • No confirmatory study is available ^[5]
• Substance-specific management ^[5]
  • Consider nebulized sodium bicarbonate solution in symptomatic patients. ^[6]
  • No specific antidote is available.

• Characteristics ^[7]
  • Highly water-soluble irritant
  • Colorless
  • Strong irritating odor
• Sources of exposure ^[7]
  • Industrial: e.g., chemical etching, microchip production, aluminum production
  • Household: e.g., cleaning products
• Pathophysiology: hydrogen fluoride dissociates into hydrogen cations and fluoride anions → fluoride ions penetrate tissue and bind intracellular calcium and magnesium → corrosive burning of mucous membranes, topical and systemic cytotoxicity, and/or electrolyte derangements ^[7]
• Clinical features ^[7]
  • Respiratory
    • Sore throat, rhinorrhea
    • Dyspnea, cyanosis
    • Signs of airway obstruction
    • Signs of pulmonary edema
  • Cardiovascular: arrhythmias, hypotension, cardiogenic shock
  • Neurological: dizziness, headache
  • Dermal: chemical burns
  • Ocular: irritation and ocular burns
  • Systemic: myalgias, fever
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific diagnostics ^[7]
  • Electrolytes: hypocalcemia, hypomagnesemia, hyperkalemia
  • ECG: Monitor for prolonged QT interval or wide QRS.
  • CXR: may show pulmonary edema and/or diffuse infiltrative opacities
  • No confirmatory study is available.
• Substance-specific management ^[7]
  • Decontamination
    • Don PPE that is chemical resistant
    • Ensure thorough decontamination is vital. ^[7]
  • Skin exposure
    • Rinse skin with running water for at least 20 minutes.
    • Apply 2.5% calcium gluconate gel to burns.
    • Consult a burn specialist as soon as possible.
  • Eye exposure: See “Ocular chemical burns.”
  • Inhalation injury: Consider nebulized calcium gluconate nebulization in patients with severe respiratory distress.
  • Systemic toxicity: Monitor calcium, magnesium, and potassium levels hourly if abnormal.
    • Calcium repletion
    • Magnesium repletion
    • Management of hyperkalemia

Topical and systemic calcium gluconate formulations are the treatment of choice to neutralize fluoride ions and counteract the toxic effects of intracellular calcium binding. ^[7]

Hydrogen fluoride is highly corrosive. Chemical-resistant PPE and thorough body surface decontamination are essential. ^[7]

• Characteristics ^[8]
  • Highly water-soluble irritant and asphyxiant
  • Flammable
  • Colorless
  • Rotten-egg odor
• Sources of exposure ^[8]
  • Industrial: e.g., petroleum and gas industry, sulfur mining, sewage treatment plants, waste disposal
  • Natural environment: e.g., swamps, hot springs, volcanoes
• Pathophysiology ^[8]
  • Inhibition of mitochondrial cytochrome oxidase → neurotoxicity, cardiotoxicity, lung toxicity
  • Irritation of the skin and mucous membranes (e.g., eyes, respiratory tract)
• Clinical features ^[8][9]
  • CNS: headache, seizures, respiratory paralysis, altered mental status or coma
  • Respiratory: upper airway irritation, cough, dyspnea, acute lung injury, pulmonary or bronchial hemorrhage
  • Cardiac: arrhythmias, conduction disturbances, myocardial ischemia, hypotension, signs of heart failure
  • Dermal: burning, itching, erythema
  • Ocular: keratoconjunctivitis
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific diagnostics ^[9]
  • Laboratory studies: lactic acidosis
  • ECG: to evaluate for arrhythmia, conduction abnormality, or ischemia
  • CXR: may show pulmonary edema
  • No confirmatory study is available.
• Substance-specific management ^[8]
  • Consider hyperbaric oxygen therapy for severe poisoning.
  • Consider nitrite therapy (with amyl nitrite and sodium nitrite) in consultation with poison control.
  • No specific antidote is available.

This section provides an overview of nitric oxide and nitrogen dioxide poisoning; nitrous oxide is used as an anesthetic and has a different toxicity profile.

• Definition: a group of gaseous oxides that contain nitrogen; includes nitric oxide and nitrogen dioxide ^[10]
• Characteristics ^[1][10]
  • Nitric oxide: chemical asphyxiant; colorless and odorless at room temperature
  • Nitrogen dioxide: poorly water-soluble irritant; red-brown at room temperature, sharp odor ^[10]
• Sources of exposure
  • Industrial: engine exhausts, electric arc welding
  • Decomposition of silage (silo filler's disease) ^[11]
• Pathophysiology ^[10]
  • Nitric oxide
    • Potent inducer of methemoglobinemia
    • Unstable in air and undergoes oxidation to nitrogen dioxide
  • Nitrogen dioxide: comes into contact with water in the respiratory tract → production of nitric and nitrous acids and formation of toxic free radicals → irritation and/or burning of distal bronchi and alveolar damage
• Clinical features: Immediate symptoms (e.g., cough, nausea) may be followed by a symptom-free period (3–30 hours) before the onset of chemical pneumonitis.
  • Respiratory: cough, pulmonary edema, hypoxemia, dyspnea, bronchospasm
  • Dermal: chemical burns
  • Ocular: irritation and ocular burns
  • Gastrointestinal: nausea, abdominal pain
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific diagnostics ^[10]
  • Laboratory studies: ↑ methemoglobin levels for nitric oxide exposure
  • Confirmatory study: measure urine nitrogen oxide metabolites
• Substance-specific management ^[10]
  • Consider methylene blue (off-label) for patients with signs of hypoxia (other than cyanosis) or methemoglobin levels > 30%.
  • If the patient continues to worsen, consider exchange transfusion with specialist guidance.
  • No specific antidote is available.
• Complications
  • Bronchiolitis obliterans
  • ARDS

• Characteristics ^[12]
  • Irritant
  • Colorless
  • Acrid odor
• Sources of exposure
  • Ground-level ozone: smog (e.g., exhaust gases, fossil-fuel burning), industrial processes (e.g., water purification, bleaching)
  • Iatrogenic: exposure during ozone therapy
  • Natural environment: atmospheric ozone
• Pathophysiology: oxidation of biomolecules (e.g., antioxidants, proteins, carbohydrates) → oxidative damage → inflammatory response ^[13][14]
• Clinical features
  • Sore throat, dyspnea, cough, chest pain
  • Signs of AECOPD exacerbation and/or signs of asthma exacerbation ^[14]
• Diagnostics: clinical diagnosis ^[14]
• Management: Manage concomitant acute asthma exacerbation and/or COPD exacerbation. ^[14]

• Characteristics ^[15]
  • Poorly water-soluble irritant
  • Colorless
  • Hay-like odor ^[15]
• Sources of exposure ^[15]
  • Industrial: e.g., plastic production, pesticides
  • Household: e.g., paint removers, dry-cleaning agents (when exposed to heat or fire)
• Pathophysiology ^[15]
  • Direct cellular toxicity → increased capillary permeability → decreased plasma volume
  • Contact with tissue moisture → hydrolysis and formation of hydrochloric acid → damage to bronchioles and alveoli and systemic inflammatory response
• Clinical features: Immediate respiratory symptoms may be followed by a symptom-free period (up to 48 hours) before the onset of cardiorespiratory collapse. ^[15][16]
  • Respiratory: dyspnea, cough, cyanosis, signs of pulmonary edema
  • Cardiovascular: hypotension, bradycardia (early symptom), tachycardia (late symptom), cyanosis
  • Dermal: irritation, erythema
  • Ocular: tearing, corneal clouding
  • Gastrointestinal: nausea, vomiting
  • Renal: clinical features of acute kidney injury ^[15]
  • Hepatic: clinical features of acute liver failure ^[15]
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific diagnostics ^[15]
  • ECG: to monitor for dysrhythmias
  • CXR: may show pulmonary edema, hilar enlargement, and central patchy infiltrates
  • No confirmatory study is available.
• Substance-specific management ^[15]
  • Consider IV corticosteroids for patients with severe symptoms or prophylactically in patients with high-dose exposure.
  • No specific antidote is available.

• Characteristics
  • Chemical asphyxiant
  • Colorless
  • Decaying fish-like or garlic-like odor ^[17]
• Sources of exposure: pest control fumigants ^[17]
• Pathophysiology: directly inhibits mitochondrial enzymes and protein synthesis within heart and lung cells ^[17]
• Clinical features ^[17]
  • Cardiovascular: dysrhythmia, chest pain, signs of cardiogenic shock
  • Respiratory: dyspnea, symptoms of ARDS
  • Gastrointestinal: nausea, vomiting
  • Neurological: tremors, paresthesias
  • Renal: clinical features of acute kidney injury
  • Hepatic: jaundice, hepatomegaly ^[17]
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific diagnostics ^[17]
  • Troponin: to evaluate for myocardial damage
  • LFTs: to evaluate for liver injury
  • ECG: to evaluate for arrhythmias
  • CXR: may show diffuse infiltrates
  • Confirmatory study: measure urine phosphine metabolites
• Substance-specific management ^[17]
  • Manage cardiogenic shock.
  • Consider hemodialysis if renal failure develops.
  • No specific antidote is available.

• Properties
  • Solid fumigant
  • Releases phosphine gas (actual toxic agent) on contact with moisture or gastric acid
  • Garlicky or decaying fish-like odor
• Sources of exposure: fumigant tablets used for pest control
• Substance-specific diagnostics: silver nitrate paper test
  • Exposure of silver nitrate–impregnated filter paper to gastric aspirate or breath
  • Positive result: paper turns black due to formation of silver phosphide/metallic silver
• Initial management: Follow the approach to asphyxiant and irritant exposure.
• Substance-specific management
  • No specific antidote is available.
  • Magnesium sulfate may be used as an adjunct in selected cases, particularly arrhythmias, but it is not curative

• Definition: a group of fine particle or aerosolized chemicals in the form of smoke, fog, or solution that act as irritants; includes 2-chloroacetophenone (CN or “mace”), 2-chlorobenzylidene malononitrile (CS gas), and oleoresin capsicum (OC or “pepper spray”) ^[18][19]
• Sources of exposure ^[18][19]
  • Encounters with law enforcement
  • Military training or chemical warfare
  • Interpersonal violence and/or self-defense
• Pathophysiology: interaction with sensory nerve endings and inflammatory pathways → pain and tissue inflammation ^[18][19]
• Clinical features ^[18][19]
  • Ocular: pain, photophobia, conjunctivitis, lacrimation, periorbital edema
  • Respiratory
    • Most common: rhinorrhea, chest pain, dyspnea, cough
    • Prolonged exposure or high concentrations: bronchospasm, laryngospasm, pneumonitis, pulmonary edema
  • Dermal: burning sensation, blistering, erythema, chemical burns
  • Gastrointestinal: nausea, vomiting, diarrhea
• Diagnosis: clinical diagnosis
• Management ^[18][19]
  • Treat the patient in a well-ventilated room.
  • Remove contaminated clothing.
  • Provide symptom-based management, e.g.:
    • Eye flushing with saline or water for 15–20 minutes
    • Copious skin irrigation with soap and water
    • Treatment of contact dermatitis and/or treatment of burns
    • Manage concomitant acute asthma exacerbation and/or COPD exacerbation.
    • Antiemetic therapy and fluid resuscitation

Perform an eye examination for suspected eye injury from exposure to tear gas, explosions, and/or traumatic eye injuries from shrapnel (e.g., tear gas grenades). ^[18]

• Properties: colorless, odorless gas; simple asphyxiant
• Sources of exposure ^[20]
  • CO₂ narcosis (e.g., due to COPD)
  • Sublimation of dry ice
  • Increased production during fermentation processes, e.g., in grain silos, wells, sources of geothermal emissions
• Clinical features
  • In atmospheric concentrations < 0.3%: no health risks
  • In atmospheric concentrations of 5–8%: headaches, vertigo, dyspnea and tachypnea, tachycardia and arrhythmias, impaired consciousness
  • In atmospheric concentrations > 8%: tremors, sweating, diminished hearing, loss of consciousness, respiratory depression, respiratory arrest ^[21]
• Management ^[22]
  • Remove the patient from the source of carbon dioxide poisoning.
  • Provide respiratory support, including oxygen therapy and mechanical ventilation, if necessary.

• Properties
  • Clear, colorless, fuming liquid
  • Corrosive irritant and oxidizing mineral acid
  • Turns yellow-brown on exposure to light and/or air
• Source of exposure
  • Industrial manufacturing (e.g., explosives, fertilizers, dyes, metallurgy)
  • Intentional assault
• Pathophysiology
  • Nitrates the aromatic rings of amino acids (e.g., tyrosine, tryptophan) in tissue proteins → production of yellow nitro-proteins, with stable, yellow staining (xanthoproteic reaction)
• Clinical features
  • Permanent yellow to yellow-brown discoloration of the skin, teeth, and mucosa
  • Corrosive injury at the site of contact
  • Ingestion: coffee-ground/bloody vomitus, burning pain, dysphagia, abdominal pain, shock, and possible perforation/stricture
  • Inhalation: cough, sore throat, laryngeal edema, chemical pneumonitis, delayed pulmonary edema

• Properties
  • Heavy, odorless, colorless, and oily liquid
  • Strongly corrosive, hygroscopic mineral acid
• Source of exposure
  • Industrial manufacturing (e.g., lead-acid batteries, fertilizers, chemical synthesis)
  • Household agents (e.g., drain cleaners)
  • Intentional assault
• Pathophysiology: contact with organic matter → intense hygroscopic action and exothermic reaction → coagulation necrosis followed by carbonization of tissues
• Clinical features
  • Black or dark-brown charring (charcoal-like appearance) of the skin, tongue, and stomach mucosa
  • Chalky-white teeth due to demineralization/dehydration of enamel
  • Severe corrosive injury with risk of gastric/oesophageal perforation, shock, strictures, and death
  • Inhalation: respiratory irritation, delayed pulmonary edema

• Properties
  • Non-metallic irritant
  • Toxic, waxy solid
  • Phosphorescent
  • Ignites spontaneously on exposure to air
• Sources of exposure: fireworks, explosives, rodenticides, fertilizer industries, and occupational inhalation exposure
• Acute poisoning
  • Stage 1: severe gastroenteritis with vomiting that may be luminous in the dark, smoky or garlic-like odor of breath, vomitus, or stools
  • Stage 2: asymptomatic latent phase, which may falsely suggest clinical improvement
  • Stage 3: progression to hepatic failure, shock, and multiorgan failure
• Chronic poisoning: Occupational exposure can cause phossy jaw, which is characterized by painful mandibular osteomyelitis/osteonecrosis with swelling, draining sinuses, and a foul garlic-like odor.