Toxic inhalation

Background

• Toxic inhalation injury encompasses pulmonary and systemic damage from inhaling noxious gases, fumes, vapors, or smoke.
• It is the leading cause of death in fire-related injuries and accounts for over 125,000 ED visits annually from chemical inhalation alone in the United States. The water solubility of the inhaled agent is the single most important determinant of injury location and symptom timing — a concept critical for ED disposition decisions. Delayed pulmonary edema occurring hours after exposure in an initially asymptomatic patient is the most dangerous pitfall.
• Three zones of injury:
  • Supraglottic (thermal/upper airway): Direct heat injury; steam carries 4000× the heat capacity of dry air; causes edema, erythema, and mucosal sloughing → progressive airway obstruction over 12–24 hours
  • Tracheobronchial (chemical/lower airway): Chemical irritation from inhaled toxins → epithelial damage, bronchospasm, mucosal sloughing, cast formation, impaired mucociliary clearance
  • Alveolar/parenchymal (systemic/gas exchange): Damage to alveolar-capillary membrane → noncardiogenic pulmonary edema, V/Q mismatch, ARDS; also systemic asphyxiant effects (CO, HCN)
• The water solubility principle — the most important clinical concept:

Solubility	Injury Location	Symptom Onset	Key Agents	Clinical Implication
High	Upper airway (nose, pharynx, larynx)	Immediate (seconds to minutes) — early warning drives patient to escape	Ammonia, hydrogen chloride, sulfur dioxide, hydrogen fluoride, acrolein	Upper airway obstruction; if asymptomatic after 6h observation → low risk of delayed injury
Intermediate	Upper AND lower airways	Minutes to hours — partial early warning	Chlorine, isocyanates	Both upper airway symptoms AND potential for delayed lower airway injury/pulmonary edema
Low	Distal airways and alveoli	DELAYED (hours to 48h+) — little or no early warning	Phosgene, nitrogen dioxide (NOx), ozone	The most dangerous group — patient may be asymptomatic at presentation then develop fulminant pulmonary edema hours later; requires prolonged observation

• Smoke inhalation is a mixed exposure — contains thermal injury + highly soluble irritants (HCl, SO₂, acrolein, ammonia) + systemic asphyxiants (carbon monoxide, hydrogen cyanide)
• Burning plastics, rubber, and synthetic materials produce phosgene, HCN, isocyanates, and acrolein — far more toxic than burning wood alone
• Household chemical mixtures: Bleach (hypochlorite) + ammonia → chloramine gas; bleach + acid → chlorine gas — common accidental exposures
• Key specific agents:
  • Phosgene (COCl₂): Odor of freshly mown hay; used in chemical synthesis (isocyanates, pesticides); produced when chlorinated hydrocarbons are heated/welded; WW1 chemical weapon (80% of chemical warfare deaths); latent period 30 min to 48 hours before fulminant pulmonary edema; no antidote
  • Nitrogen dioxide (NO₂): Silo filler's disease (silage generates NOx in first 10 days); also welding, electroplating, ice resurfacing (Zamboni) machines; triphasic illness — (1) initial mild irritation, (2) delayed chemical pneumonitis/pulmonary edema at 24–72h, (3) bronchiolitis obliterans at 2–6 weeks
  • Chlorine (Cl₂): Pool chemicals, water treatment, industrial; intermediate solubility → both upper and lower airway injury; noncardiogenic pulmonary edema in severe exposures
  • Ammonia (NH₃): Highly soluble → immediate upper airway burns; forms ammonium hydroxide (alkali) on mucous membranes → liquefactive necrosis; massive exposure can cause laryngospasm and pulmonary edema
  • Hydrogen sulfide (H₂S): "Knockdown gas"; rotten egg odor (olfactory fatigue at high concentrations — cannot smell it); mitochondrial toxin (inhibits cytochrome oxidase like cyanide); may cause sudden collapse and death
• Metal fume fever: Zinc oxide fume inhalation (welding galvanized steel); self-limited flu-like illness 4–12 hours after exposure; not true toxic injury but frequently presents to ED
• Reactive airways dysfunction syndrome (RADS): New-onset persistent asthma-like syndrome following single high-dose irritant inhalation exposure; may be permanent
• Long-term sequelae: Bronchiolitis obliterans, bronchiectasis, RADS, pulmonary fibrosis, tracheal/bronchial stenosis

Clinical Features

Upper airway (thermal/highly soluble agents):

• Facial burns, singed eyebrows/nasal hairs, soot in nares or oropharynx
• Hoarseness, stridor, dysphonia
• Oropharyngeal erythema, edema, blistering
• Drooling, dysphagia
• Airway obstruction may be progressive — can worsen dramatically over 12–24 hours as edema develops; a patient with mild hoarseness on arrival may have complete obstruction hours later

Lower airway (chemical irritants):

• Cough (initially dry, may become productive with soot-stained or blood-tinged sputum)
• Bronchospasm/wheezing
• Dyspnea, tachypnea
• Chest tightness
• Hypoxemia

Alveolar/parenchymal:

• Progressive hypoxemia
• Noncardiogenic pulmonary edema (frothy sputum, bilateral crackles)
• ARDS
• May be DELAYED hours to days — particularly with phosgene and nitrogen dioxide

Systemic asphyxiant effects (smoke inhalation):

• Carbon monoxide poisoning: Headache, confusion, nausea, cherry-red skin (unreliable), syncope, seizures, coma, cardiac ischemia; CO-oximetry required (standard pulse oximetry is falsely normal)
• Cyanide toxicity: Altered mental status, lactic acidosis, cardiovascular collapse; suspect in all enclosed-space fire victims with persistent lactic acidosis despite O₂ therapy

Other:

• Conjunctival irritation, chemical keratitis (especially ammonia, chlorine, H₂S)
• Dermal burns (ammonia, HF, phosgene in liquid form)
• GI symptoms: nausea, vomiting (especially H₂S, metal fume fever)
• Hydrogen sulfide: Sudden loss of consciousness ("knockdown"), seizures, apnea, cardiac arrest — may be the presenting event with no preceding symptoms at high concentrations

Differential Diagnosis

• Anaphylaxis (bronchospasm, hypotension without inhalation history)
• Asthma or COPD exacerbation
• Pneumonia or aspiration pneumonitis
• Pulmonary embolism
• Acute coronary syndrome (CO poisoning causes myocardial ischemia)
• Cardiogenic pulmonary edema
• Sepsis (delayed presentation of toxic inhalation can mimic sepsis)
• Aspiration of gastric contents
• Thermal airway burns without chemical component
• Panic attack/hyperventilation (diagnosis of exclusion in exposure setting)

Toxic gas exposure

• Carbon monoxide toxicity
• Chemical weapons
• Cyanide toxicity
• Dichloromethane toxicity
• Hydrocarbon toxicity
• Hydrogen sulfide toxicity
• Inhalant abuse
  • Difluoroethane toxicity
• Methane toxicity
• Smoke inhalation injury
• Ethylene dibromide toxicity

Evaluation

Workup

History — critical questions:

• What was inhaled? (specific agent, if known; or type of fire/materials burning)
• Where? Enclosed space → much higher risk of CO and HCN; high-dose parenchymal injury
• Duration of exposure
• Loss of consciousness at scene? (suggests significant CO or HCN exposure)
• Use of respiratory protection?
• Pre-existing pulmonary disease (asthma, COPD)?
• Occupational context (welding, farming/silo, pool chemical mixing, industrial setting)

Physical exam — focused assessment:

• Complete upper airway exam: oropharynx for soot, erythema, edema, blistering
• Facial/nasal hair singeing
• Voice quality (hoarseness = laryngeal involvement)
• Lung auscultation: wheezing, crackles, stridor, decreased breath sounds
• Associated burn assessment (% TBSA, depth)
• Neurologic status (CO/HCN)

Laboratory:

• CO-oximetry (ABG or VBG with co-oximetry): Mandatory in all smoke inhalation; standard pulse oximetry does NOT detect carboxyhemoglobin (SpO₂ reads falsely normal)
• Lactate: Elevated lactate with high-flow O₂ → suspect cyanide toxicity (lactate >8 mmol/L is highly suggestive)
• ABG/VBG: PaO₂, PaCO₂, pH, A-a gradient
• CBC, BMP, troponin (CO causes myocardial injury)
• Methemoglobin level (co-oximetry) — if nitrate/nitrite exposure suspected
• Serum cyanide level: Takes too long to guide acute management — treat empirically based on clinical suspicion; do not wait for results
• Serum ethanol, toxicology screen (fire victims may have concomitant intoxication)

Imaging:

• Chest X-ray: Often initially normal — this does NOT rule out significant inhalation injury; delayed pulmonary edema may develop hours later
• Serial CXR at 6h, 12h, 24h for significant exposures
• CT chest: more sensitive; may show ground-glass opacities, peribronchial thickening; not routinely obtained acutely unless diagnosis uncertain
• CT face/neck if concern for deep thermal airway injury

Bronchoscopy (coordinate with pulmonology/ICU):

• Gold standard for assessing lower airway injury severity
• Findings: mucosal erythema, edema, soot deposits, ulceration, necrosis, carbonaceous material
• Helps guide intubation decisions and predict need for ventilatory support

Other:

• EKG: All smoke inhalation patients (CO → myocardial ischemia, dysrhythmias)
• Continuous pulse oximetry AND end-tidal CO₂ monitoring
• Peak flow or bedside spirometry (if bronchospasm assessment needed)

Diagnosis

• Primarily clinical — based on exposure history + compatible symptoms + physical findings
• No single diagnostic test confirms or excludes inhalation injury
• High index of suspicion required for low-solubility agents (phosgene, NOx) where patients may be initially asymptomatic
• CO-oximetry confirms CO exposure; elevated lactate with normal PaO₂ suggests HCN
• Normal initial CXR does NOT exclude significant injury — serial imaging is essential

Management

Airway — the #1 priority:

• Intubate early if any concern for progressive airway compromise — the window to secure the airway may be narrow; waiting for desaturation is too late
• Indications for intubation:
  • Respiratory distress, stridor, hoarseness with progression
  • Blistering or edema of oropharynx
  • Deep facial or neck burns
  • Hypoventilation, obtundation
  • GCS ≤8
  • Progressive hypoxemia despite high-flow O₂
• Use the largest ETT possible (6.5–8.0) — airway edema will worsen, and a large tube facilitates suctioning of casts and secretions
• Consider awake fiberoptic intubation if airway anatomy is distorted
• Avoid nasal intubation in facial burns (mucosal fragility)
• Cricothyrotomy if oral intubation fails

Oxygen:

• 100% FiO₂ via non-rebreather for ALL smoke inhalation patients until CO is excluded
• CO half-life: room air ~320 min; 100% NRB ~60–90 min; hyperbaric O₂ ~20–30 min
• Continue high-flow O₂ until COHb <5% and symptoms resolve

Carbon monoxide:

• See carbon monoxide poisoning for full management
• Hyperbaric oxygen (HBO) indications remain controversial; consider for: loss of consciousness, neurologic symptoms, COHb >25%, pregnancy, myocardial ischemia, persistent symptoms despite NRB

Cyanide:

• See cyanide toxicity for full management
• Hydroxocobalamin (Cyanokit) 5g IV — preferred antidote; safe to give empirically in enclosed-space fire with altered mental status + lactic acidosis; does not affect CO-oximetry readings
• Sodium thiosulfate is an alternative but slower acting
• Do NOT use nitrite-based cyanide antidotes (amyl nitrite, sodium nitrite) in smoke inhalation — they induce methemoglobinemia, which is dangerous in patients with concurrent CO poisoning (both COHb and MetHb impair O₂ delivery)

Bronchospasm:

• Inhaled beta-agonists (albuterol) and ipratropium
• Severe: IV magnesium, epinephrine
• Nebulized sodium bicarbonate (NaHCO₃ 3.75%) has been used for chlorine and acid gas exposures — limited evidence but may help neutralize acid deposits in airways

Agent-specific management:

Agent	Key Management Points	Observation Time
Smoke (fire)	100% O₂; CO-oximetry; hydroxocobalamin if HCN suspected; early intubation for airway edema; burn center transfer if burns present	24h minimum if enclosed-space exposure
Chlorine	Beta-agonists; O₂; observation for delayed pulmonary edema; humidified O₂; NaHCO₃ nebs may help	≥6 hours if symptomatic; 24h if significant exposure
Ammonia	Copious irrigation of eyes/skin; bronchodilators; early intubation for laryngeal edema; fluids CAUTIOUSLY (pulmonary edema is noncardiogenic — patients may be hypovolemic); diuretics usually contraindicated	6–12 hours minimum
Phosgene	NO ANTIDOTE; avoid exertion (increases pulmonary blood flow → accelerates edema); supportive care for pulmonary edema; lung-protective ventilation; diuretics contraindicated (noncardiogenic edema, patients are hypovolemic); respiratory distress within 4h of exposure = probable LD₅₀ dose	24–48 hours minimum (up to 72h)
Nitrogen dioxide (silo filler's)	Supportive; corticosteroids may prevent delayed bronchiolitis obliterans (limited evidence); monitor for triphasic illness — initial symptoms, delayed pneumonitis (24–72h), then BO (2–6 weeks)	24–48 hours; warn about delayed BO at 2–6 weeks
Hydrogen sulfide	Remove from exposure (rescuers need SCBA — do not enter without PPE); high-flow O₂; nitrite antidotes (sodium nitrite or amyl nitrite) MAY be used (unlike in CO+HCN coexposure); cardiac monitoring for arrhythmias; HBO may help	24h if symptomatic; treat like CO + CN combined
Metal fume fever (zinc oxide)	Self-limited; NSAIDs, fluids, observation; resolves in 24–48h	Brief observation if mild; usually can discharge

General supportive care:

• IV access, cardiac monitoring, continuous pulse oximetry
• Lung-protective ventilation if intubated (6 mL/kg IBW; PEEP as needed)
• Aggressive pulmonary toilet — frequent suctioning for cast and secretion management
• Avoid fluid overload — pulmonary edema from inhalation injury is noncardiogenic (permeability-based); excessive fluids worsen it
• Steroids: Not routinely recommended for smoke inhalation (increase infection risk, impair wound healing); may be considered for refractory bronchospasm, nitrogen dioxide-induced BO, or patients on chronic steroids
• Decontamination: Skin/clothing decontamination if external chemical exposure; remove contaminated clothing; healthcare workers may be at risk from off-gassing — use appropriate PPE

Disposition

• Admit (ICU):
  • Intubated patients or those with high risk of progressive airway compromise
  • Significant smoke inhalation with enclosed-space exposure
  • Abnormal CO-oximetry (COHb >15% symptomatic, >25% asymptomatic)
  • Suspected cyanide toxicity
  • Pulmonary edema or significant hypoxemia
  • Phosgene or nitrogen dioxide exposure with any symptoms
  • Hydrogen sulfide exposure with syncope or altered mental status
  • Concurrent burns requiring burn center care
• Admit (observation):
  • Symptomatic chlorine or ammonia exposure with improving symptoms — observe minimum 6h (some recommend 12–24h for ammonia)
  • Any exposure to low-solubility agents (phosgene, NOx) — observe 24–48 hours minimum even if asymptomatic at presentation
  • Moderate smoke inhalation without concurrent CO/HCN toxicity
• Discharge (with precautions):
  • Asymptomatic patients with exposure to highly soluble agents only (ammonia, HCl, SO₂) who remain asymptomatic after 6 hours of observation with normal exam and normal CXR
  • Metal fume fever with mild symptoms and improving
  • Minor smoke exposure in open/well-ventilated space with normal CO-oximetry and no symptoms
  • Critical discharge instructions:
    • Return immediately for any new dyspnea, cough, chest tightness, or breathing difficulty — delayed pulmonary edema may occur hours to days later
    • Avoid exertion for 24–48 hours (especially after phosgene — exertion accelerates pulmonary edema)
    • Follow up with PCP or pulmonology within 48–72 hours
    • For nitrogen dioxide: warn about delayed bronchiolitis obliterans at 2–6 weeks — return for new cough, dyspnea, or wheezing
    • Occupational health referral and OSHA reporting as appropriate
    • Smoking cessation

See Also

• Carbon monoxide poisoning
• Cyanide toxicity
• Smoke inhalation
• Chlorine gas
• Hydrogen sulfide toxicity
• ARDS
• Burns
• Chemical burns
• Metal fume fever
• Methemoglobinemia

External Links

• Nitrogen Dioxide Toxicity — StatPearls
• Phosgene: Medical Management — CHEMM/HHS
• Ammonia: Medical Management — CHEMM/HHS
• Smoke Inhalation Injury — Medscape
• Acute Inhalation Injury — PMC Review
• Inhalation Injuries — Taming the SRU