Inhalational InjuriesYael Moussadji, PGY 4Apr 10, 2008

Sources of Exposure

Industry/occupational

Home/community

War/chemical weapons

Classification of Injury

Direct pulmonary toxicity

Irritant or inflammatory response

Systemic toxicity

simple and chemical asphyxiants

organophosphates

hydrocarbons

metal fumes

Mechanism of ToxicityExposure level

Water solubility

Particle size

Cell injury and inflammation

Mixtures

Host factors

Exposure level

Controlled vs uncontrolled (explosion)

Confined vs outdoors or ventilated area

Duration of exposure

Water SolubilityPlays a significant role in determining the location of injury

Gases that are highly water soluble (ammonia, sulfur dioxide, HCl) usually cause acute irritant injury to the mucus membranes (eyes, nares, upper airway), sparing the lower respiratory tract; immediately symptomatic

Compounds that are less water soluble (phosgene, ozone, nitrogen dioxides) often cause no symptoms in the upper airway and easily penetrate into the lower airway, causing delayed irritant effects at the bronchi, terminal bronchioles, and alveoli

Increases risk for poor outcomes since agents may not be immediately symptomatic, increasing duration of exposure

Gases of intermediate solubility (chlorine) can exert irritant effects throughout the respiratory tract

Particle Size

Principle contributor to airway penetration

Particles greater than 10 microns are filtered in the nose and/or deposited on the larynx

Particles less than 10 microns are deposited in the large airways, and those less than 5 microns are deposited in the distal airways and alveoli

Cell injury and inflammation

Irritants damage cells in a non-immunologic fashion, causing cellular injury (acids, alkalis, reactive oxygen species)

Temperature can also cause direct injury, most often to the upper resp tract; steam inhalation can transfer heat and cause injury deep in the resp tract (heat capacity 4000 times greater)

Mixtures

Mixtures of substances can act synergistically on cells and tissue

Smoke contains multiple substances of combustion, leading to potentially severe inhalational injury

Mixing cleaning solutions can cause chemical byproducts

Injury Patterns

Simple asphyxiation

Tissue asphyxiation

Non-respiratory systemic toxicity with pulmonary absorption

Direct cellular injury

Simple Asphyxiation

Nitrogen, helium, hydrogen, methane, propane, natural gas displace O2

Otherwise essentially inert

Tissue Asphyxiants

CO, hydrogen cyanide, hydrogen sulfide

Inhibits mitochondrial electron transport and oxygen use

Systemic Toxicants

Usually cause no direct airway or lung injury

Halogenated hydrocarbons, benzene, solvents, metals

Direct injury

loss of airway patency secondary to mucosal edema

bronchospasm secondary to inhaled irritants

intrapulmonary shunting from small airway occlusion, mucosal edema, sloughed endobronchial debris

diminished compliance secondary to alveolar flooding and collapse, and V/Q mismatch

pneumonia and tracheobronchitis due to loss of ciliary clearance

respiratory failure and ARDS

Clinical Assessment

Upper airway injury

ranges from simple transient irritation to airway compromise

Conducting airway injury

bronchoconstriction

Lower respiratory tract injury

pneumonitis, pulmonary edema

Cough (most common), wheeze, dyspnea, hypoxemia

Systemic effects (tissue asphyxiants) can cause dizziness, headache, chest pain, nausea and vomiting, altered mental status

DiagnosisParenchymal lung injury evolves over time and is often minimal at first

Suspect if historical risk factors (exposure in enclosed space or to byproducts of combustion) and physical signs (carbonaceous sputum, singed nasal hairs)

CXR often initially normal, assess for bronchial wall thickening

ABG (co-oximetry)

Spirometry or peak flows can give a general picture of airflow dynamics

Direct visualization with fiberoptic laryngoscopy or bronchoscopy to assess airway injury severity

Case 1

37 y/o f, PMHx exercise induced asthma

Cleaning her bathroom with a combination of bleach and disinfectants

Sudden onset of a strong odor

Developed marked irritation of eyes and burning sensation in nose and throat

Immediately left the bathroom

Feels nauseated and slightly dyspneic

Case 1

Vitals: HR 87, RR 22, BP 112/76, T 37.1, SpO2 98% on R/A

Mild conjunctivitis and rhinitis

Diffuse expiratory wheeze throughout

Exam otherwise normal

CXR normal

Peak flows 60% predicted prior to treatment

Pulmonary Irritants:Household Toxins and Occupational Exposures

Certain household cleaning products can cause acute inhalational injury when mixed

Hypochlorite, an oxidizer, is a component of household bleach cleaners (concentrations <6%)

Mixing hypochlorite solutions with acids, such as hydrochloric acid or phosphoric acid cleaning powders, generates chlorine; mixing hypochlorite solutions with ammonium hydroxide containing solutions generate chloramine; both are irritant gases

Chlorine

Greenish-yellow gas involved in many industrial processes such as water disinfection and paper production

Mixing of cleaning solutions and powders may also result in chlorine exposures of janitorial workers

Strong irritant and odor effects

Intermediate water solubility resulting in irritant effects throughout the resp tract

Severity of effect related to duration and intensity of exposure

Ammonia

Anhydrous ammonia is a colourless gas with a strong odor

Generally stored under pressure as a liquid

Used widely in industry and agriculture

Highly water soluble, upper resp tract usually affected first with immediate irritation of eyes and mucus membranes

Affinity for mucus membranes leading to liquifactive necrosis and full thickness tissue destruction

Inhalation causes hemoptysis, pharyngitis, pulmonary edema, bronchiectasis

Sulfur DioxideByproduct of combustion of sulfur containing fossil fuels

Major sources include oil and coal-fired power plants

Also used as a bleaching agent in industrial processes such as paper and textile bleaching, fruit preservative, and agricultural fumigants

Major component of smog

Highly water soluble, exerting irritant effects on mucus membranes and upper airway

Reaction of sulfur dioxide with water produces sulfuric acid, causing local tissue destruction

Industry at Risk

Semiconductor manufacturing

Plastic manufacturing

Mining

Agriculture

Construction

Other agentsHydrofluoric acid

Commercial processes; causes severe burns and systemic hypocalcemia

Ozone

Water purification, photocopy machines; insoluble in water, generates oxygen free radicals, characteristic odor similar to chlorine bleach

Phosgene

carbonic acid dichloride; colourless gas, smells like hay, used in production of pesticides; oxidant properties and low water solubility

Severe pulmonary edema can develop over several hours

Pulmonary Irritants: ManagementSigns of upper airway dysfunction mandate visualization of the larynx

Bronchospasm generally responds well to inhaled beta-adrenergic agnonists

Nebulized 2% bicarb can provide relief for patients exposed to chlorine or HCL gas

Presence of ALI or ARDS necessitates aggressive supportive care

Patients exposed to highly water soluble agents can be discharged if they are asymptomatic or improve with supportive care

After exposure to intermediate or poorly water soluble agents, patients should be observed for increasing dyspnea for several hours or admitted

Case 2

49 y/o male arrives to ED with c/o H/A and dizziness

Was working in the garage cleaning paint brushes and noticed an insidious onset of feeling unwell

O/E: All VS normal, slightly unsteady on feet

Now feeling slightly better

Methylene Chloride and Halogenated HydrocarbonsComponent of pain remover, pain thinner, and other solvents

Methylene chloride and other hydrocarbons exert systemic toxicity following pulmonary absorption

CNS depression and hepatotoxicity, causing dizziness, H/A, ataxia, abdo pain, coma, apnea, dysrhythmias

Complications include aspiration pneumonia, chemical hepatitis, and hypoxic encephalopathy

Methylene chloride is metabolized to CO, further contributing to toxicity

Case 3

55 y/o m construction worker

Involved in explosion, thrown backward 10 feet

Second and third degree burns to face, neck, torso, arms and legs

Comes in with EMS on backboard in collar, alert and screaming in pain

VSS

Case 3

Case 3

While you are setting up the scope, he begins to complain of difficulty breathing and becomes increasingly stridorous...

What the *#&%^ do you do now?

Smoke Inhalation InjuryMost like cause of acute inhalation injury in the ED

Mortality rates from smoke inhalation alone are 5-8%

Mortality rates of combined major burn injury and inhalation injury exceed that of either alone

Inhalation injury is a predictor of prolonged ventilator dependence and death

Twenty percent of those requiring admission to a burn unit carry a diagnosis of inhalation injury

Inhalation injury represents a combination of airway injury, direct pulmonary injury and metabolic toxicity

Clinical CourseEarly death is caused by asphyxia, airway compromise, or metabolic poisoning: early visualization of the airway is crucial

Early resuscitation phase is characterized by acute pulmonary insufficiency +/- critical airway narrowing that can progress over 18-24 hours

Post-resuscitation phase is 2-5 days and is characterized by mucosal necrosis, secretions, distal airway obstruction with atelectasis, pulmonary interstitial edema, and bronchopneumonia

Inflammatory-infection phase at 5 days and beyond continues until there is lung healing and burn wound closure; no role for prophylactic antibiotics

Two principle components: direct lung injury and systemic smoke inhalation syndrome

Smoke Lung InjuryTypically irritant in nature

Gas phase constituents include CO, hydrogen cyanide, acid and aldehyde gases, oxidants

Toxicity depends on the fuel burning, completeness of combustion, and generated heat intensity

Clinical consequences depend on chemical composition, particulate size, exposure time, minute ventilation

Inflammatory effects causing capillary leak are complimentary; cutaneous burns increase the degree of pulmonary capillary leak, and inhalation injury increases the degree of burn edema; these patients need fluid

Systemic Effects: CO Poisoning

Tissue asphyxiants released during combustion include CO and hydrogen cyanide

CO is rapidly transported across the alveolar membrane and binds preferentially to Hb, which can be directly measured by co-oximetry

HgCO shifts the oxyhemoglobin dissociation curve to the left, impairing unloading of oxygen at the tissues

With prolonged exposure, CO saturates cells and binds to cytochrome oxidase, uncoupling mitochondrial oxidative phosphorylation and decreasing APT production, resulting in metabolic acidosis

CO PoisoningMost common cause of poisoning death and most common cause of fire related death; generated through incomplete combustion of carbon containing products

CO is displaced from Hb by the administration of supplemental oxygen

The half-life of HbCO in air is 4-6 hours and inversely related to PaO2

Breathing 90-100% O2 at 1 atmosphere reduces the half-life to 60-90 min

Breathing 100% O2 at 3 atmospheres reduces the half-life to 30 min

HBO is more effective at removing CO from mitochondrial cytochromes

CO levels do not correlate with outcomes

the HBO controversycontroversy exists because for most patients, HBO is not administered as a life saving treatment, but rather to prevent neurologic sequelae

appears to reduce the rate of neurologic sequelae if administered in the early stages (<6hrs)

Weaver’s NEJM study in 2002 found that HBO administered over 3 sessions reduced the incidence of delayed neurologic sequelae at 6 weeks and 1 year, but results of other studies have been mixed or show no benefit

current recommendations include treatment for any patient with neurologic or cardiovascular compromise (seizures, coma, dysrhythmias, ischemia), severe metabolic acidosis, HbCO >25% or >10-15% in pregnancy (greater fetal Hb affinity for CO)

Hydrogen Cyanide

Hydrogen cyanide is a combustion product of natural and synthetic materials

Contribution of cyanide toxicity in acute smoke inhalation is rare and usually in association with CO poisoning

Cyanide is rapidly absorbed and distributed to tissues

Within seconds, it impairs the electron transport chain and inhibits oxidative metabolism

Poisoned tissue rapidly deletes itself of ATP, then ceases to function causing coma, seizures, cardiovascular collapse, and severe metabolic acidosis

Hydrogen Cyanide

Binds to oxidized Hb forming cyanomethemoglobin

CvO2 approaches arterial O2 because there is no oxygen extraction at the tissues

Cyanide is detoxified in the liver by sulfur transferase to thiocyanate, then excreted by the kidney, regenerating methemoglobin from cyanomethemoglobin

Surrogate marker of toxicity is lactate > 10 mmol/L refractory to treatment

ManagementGoal of therapy is to reactivate the cytochrome oxidase system by providing an alternative high affinity source of ferric ions for cyanide to bind

Nitrites are administered by inhalation (amyl nitrite) or IV infusion (sodium nitrite 300 mg over 2-4 minutes) to induce 8% methemoglobin to facilitate transport of cyanide as cyanomethemoglobin from mitochondrial cytochromes to hepatocytes

Substrate sulfur is then applied by IV administration of sodium thiosulfate (12.5g IV) to convert cyanide to thiocyanate

When oxygen transport is already compromised, as in concomitant CO poisoning, sodium thiosulfate is administered alone; in these cases it is safe and beneficial without risk of hypotension or worsening MetHb

Smoke Inhalation: take home points

Early resuscitation must include an assessment for airway obstruction from tissue edema, which can progress over 18-24 hours

Stridor, dyspnea, and increased WOB reflect critical airway narrowing: Intubate early

Initial PaO2 cannot be used to predict disease

Proceed with adequate fluid resuscitation in burned patients

Suggested approach to suspected cyanide toxicity in the setting of smoke inhalation with refractory metabolic acidosis is IV administration of 12.5 g of sodium thiosulfate

Hydrogen Sulfide

H2S poisoning occurs in petroleum refinery and sewage tank workers

Odor similar to rotten eggs

Pulmonary irritant and cellular poison

Rapidly dissociates from the mitochondria, which allows patients to survive after brief exposures

Removal from exposure (with appropriate gear) and standard resuscitation are usually sufficient to reverse toxicity

Case 4

38 y/o m welder

Welding galvanized steel all day, no mask (despite what his doctor girlfriend told him)

Complains of SOB, feeling unwell, and pain from mid chest to mid thighs

O/E: BP 124/80, RR 20, T 37.9, SpO2 93%, slight wheeze and cough

Metal Fume Fever

Non-specific flu like illness after exposure to metal oxide fumes

Mechanism of injury unknown (? immunologic)

Generally results in vague flu-like symptoms such as fever, nausea, vomiting, muscle ache, joint pain, metallic taste

Treatment is supportive, can administer O2 as needed

Symptoms usually resolve over 24-48 hours

Apparently drinking milk helps

In The End...

Inhalational injury results in either airway or pulmonary injury, or systemic toxicity

Few clinical antidotes, treatment is largely supportive

Period of observation depends on agent involved, intensity and duration of exposure

Poor prognostic indicators include progressive respiratory difficulty, rales, burns to the face, hypoxemia, and altered mental status