Inhalational Injuries

1. Inhalational Injuries • Yael Moussadji, PGY 4 • Apr 10, 2008

2. Sources of Exposure • Industry/occupational • Home/community • War/chemical weapons

3. Classification of Injury • Direct pulmonary toxicity • Irritant or inflammatory response • Systemic toxicity • simple and chemical asphyxiants • organophosphates • hydrocarbons • metal fumes

4. Mechanism of Toxicity • Exposure level • Water solubility • Particle size • Cell injury and inflammation • Mixtures • Host factors

5. Exposure level • Controlled vs uncontrolled (explosion) • Confined vs outdoors or ventilated area • Duration of exposure

6. Water Solubility • Plays 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

7. 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

8. 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)

9. 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

10. Injury Patterns • Simple asphyxiation • Tissue asphyxiation • Non-respiratory systemic toxicity with pulmonary absorption • Direct cellular injury

11. Simple Asphyxiation • Nitrogen, helium, hydrogen, methane, propane, natural gas displace O2 • Otherwise essentially inert

12. Tissue Asphyxiants • CO, hydrogen cyanide, hydrogen sulfide • Inhibits mitochondrial electron transport and oxygen use

13. Systemic Toxicants • Usually cause no direct airway or lung injury • Halogenated hydrocarbons, benzene, solvents, metals

14. 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

15. 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

16. Diagnosis • Parenchymal 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Sulfur Dioxide • Byproduct 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

23. Industry at Risk • Semiconductor manufacturing • Plastic manufacturing • Mining • Agriculture • Construction

24. Other agents • Hydrofluoric 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

25. Pulmonary Irritants: Management • Signs 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

26. 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

27. Methylene Chloride and Halogenated Hydrocarbons • Component 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

28. 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

29. Case 3

30. 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?

31. Smoke Inhalation Injury • Most 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

32. Clinical Course • Early 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

33. Smoke Lung Injury • Typically 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

34. 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

35. CO Poisoning • Most 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

36. the HBO controversy • controversy 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)

37. 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

38. 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

39. Management • Goal 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

40. 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

41. 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

42. 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

43. 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

44. 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