1. PULMONARY AGENTS
Welcome to the Pulmonary Agents lecture. This is one of a series of lectures on the medical management of chemical casualties presented by the Chemical Casualty Care Division, US Army Medical Research Institute of Chemical Defense. The major reference for this lecture is the 1997 edition of the Textbook of Military Medicine, part I, Medical Aspects of Chemical and Biological Warfare. Chapter 9 of this text, Toxic Inhalational Injury, was written by Dr. John Urbanetti, Clinical Assistant Professor of Medicine, Yale University School of Medicine. Dr. Urbanetti has extensive experience with the treatment of occupational exposure to toxic pulmonary agents.

2. OBJECTIVES Historical perspective
General issues related to toxic exposure
Agents
source
mechanism of injury
clinical effects
therapy
Lung-damaging agents ushered in the modern era of chemical warfare.
This discussion of pulmonary agents includes the traditional chemical-warfare agents chlorine and phosgene, as well as three additional compounds that produce similarly toxic injury to the lung, perfluoroisobutylene, HC smoke and oxides of nitrogen.
We’ll review their relevant threat to the US Military and American people, some basic principles of toxic pulmonary injury, the physical properties of these compounds, the proposed mechanism of toxic injury, the signs and symptoms of exposure, and the treatment of exposure to any of these compounds.

3. RELEVANCE Chlorine, Phosgene - used in industry Related compounds
mass produced and transported
industrial accidents
domestic terrorism
Related compounds
organofluoride polymers (PFIB)
oxides of nitrogen
HC smoke (zinc oxide)
While it is unlikely that an adversary would use chlorine or phosgene to attack US Forces on today’s battlefield, these agents and related compounds still pose a serious threat to The US military and the American people. Both chlorine and phosgene are ubiquitous in the chemical industry. These compounds are used as precursors for more complex chlorinated hydrocarbons, the primary components of modern plastics and dyes.
Thousands of tons of phosgene are produced, stored and transported each year in this country, creating the potential for a large-scale release from an industrial accident. The potential for domestic terrorism is also a concern. Terrorists use weapons of opportunity. Simply opening the valve on a chlorine or phosgene tank-car near a large metropolitan area could produce mass casualties.
US service members come in contact daily with the related compounds listed here. Exposure to these compounds can cause the same type of pulmonary injury as phosgene.

4. EXPOSURE SURFACE Route Surface Area Ingestion / parenteral ---
Ocular m2
Percutaneous m2
Respiratory m2
It is important to remember the significance of the respiratory tract as a route of exposure for all of the chemical warfare agents. The surface area in the lung available to chemical agent exposure is an order of magnitude greater than the surface area of the skin, making the protective mask the most important component of the chemical protective ensemble.

5. ANATOMY Upper Airway Central Airways Peripheral Airways
Naso/oropharynx to VC
Central Airways
conducting
VC to terminal bronchiole
Peripheral Airways
gas exchange
respiratory bronchiole to alveoli
The pulmonary tree may be divided into three distinct anatomical regions. The upper airway warms, filters and humidifies the inhaled air. The central airways, including the larynx, trachea and bronchi, conduct the inhaled air to the peripheral airways where gas exchange takes place.
Turbulent flow, protective reflexes and secretions in the nasopharynx protect the lung from toxic substances in the environment. Unfortunately, the nasopharynx is easily and quickly bypassed during exertion.
Airflow through the central airways is normally laminar and therefore quiet flow. Partial obstruction of these airways creates turbulent, noisy flow. Problems in the central airways, then, produce early, objective signs such as wheezing. Injury to the peripheral airways, on the other hand, is not normally accompanied by early clinical signs.

6. DETERMINANTS OF INJURY
Factors that determine nature, location, severity:
Agent Factors
physical / chemical properties (Solubility / Reactivity)
intensity of exposure (concentration x time)
Host Factors
defense mechanisms
ventilatory parameters
preexisting disease
The interaction of several factors determines whether an inhaled compound will have a toxic effect, the severity of that effect, and the location within the lung of that effect. These factors include the physical and chemical properties of the agent, the intensity of the exposure and factors associated the victim of the exposure, and host factors to include defense mechanism, ventilatory parameters, and pre-existing disease.

7. PHYSICAL/CHEMICAL PROPERTIES
Irritants
Centrally Acting
high solubility (ammonia, HCl)
high reactivity (mustard, Lewisite)
Intermediate (chlorine)
Peripherally Acting
low solubility/reactivity (phosgene, NOx, PFIB, HC)
For those agents classified as pulmonary irritants, the agent’s solubility and reactivity determine what part of the lung the agent will attack. Compounds like ammonia that are very soluble in water, dissolve rapidly on contact with the moist mucus membranes of the upper and central airways and primarily damage this part of the lung. Less soluble compounds like phosgene easily reach and damage the peripheral airways. Mustard is not very soluble in water, but is a highly reactive compound and therefore attacks the central airways. Chlorine is intermediate in its solubility and produces effects in both the central and peripheral airways.

8. INTENSITY OF EXPOSURE Concentration x Time = Ct lower concentrations
agent concentration
duration of exposure
lower concentrations
characteristic lesion
central vs peripheral
higher concentration
both central and peripheral effects
Another factor that determines the severity of toxic pulmonary injury is the intensity of the exposure, expressed as the concentration of the agent inhaled over a given time. For most exposures, the toxic effect is constant for a given CT product, which means similar effect are produced by either a short exposure to a high concentration or a long exposure to a low concentration of an inhaled compound (Haber’s Law).
Mild to moderate exposures produce the characteristic damage associated with the agent’s solubility and reactivity. For instance, phosgene produces peripheral injury and mustard produces central injury. However, higher intensity exposures to any of these agents will produce effects in both compartments. That is, severe exposure to a centrally acting agent like mustard can also produce effects in the peripheral airways, while a severe exposure to a peripherally acting agent like phosgene can produce central effects as well.

9. HOST FACTORS Defense mechanisms Ventilatory parameters
cough, sneeze, mucociliary detox / transport
Ventilatory parameters
oral breathing,  minute ventilation = increased exposure
Preexisting disease
cardiopulmonary disease
hyperreactive airways
In addition to agent properties, several host factors influence the nature and severity of pulmonary injury. The high level of exertion associated with combat or attempted escape from an agent release increases minute ventilation (rate and depth of breathing), thereby increasing the intensity of exposure as well. Increased minute ventilation is also normally accompanied by a shift from nasal to oral breathing, thus bypassing the upper-airway defense mechanisms previously discussed.
Toxic pulmonary exposure will normally have a greater impact on casualties with preexisting cardiac or pulmonary disease. About 15% of the adult population have a propensity for hyperreactive airways; individuals with a history of childhood asthma, seasonal rhinitis, or eczema, for instance. Exposure to pulmonary irritants will likely trigger bronchospasm in these individuals, thus compounding the pulmonary injury.

10. The characteristic pulmonary lesion produced by peripherally acting agents, and the final common pathway of injury from the agents discussed in this lecture, is non-cardiogenic pulmonary edema, also described as adult respiratory distress syndrome (ARDS) or “dry-land drowning”.
The picture at upper right depicts a cross-section through an alveolus, that part of the lung where gas exchange takes place. The close-up at lower right shows the thin alveolar-capillary membrane that separates the air in the alveolus from the blood in the capillaries. This membrane is thin by design to facilitate the passage of oxygen from alveolus to capillary and carbon dioxide from capillary to alveolus. Because of the hydrostatic pressure within the capillaries, serous fluid continuously leaks through the membrane into the interstitial tissue of the lung. The pulmonary lymph system normally compensates for this leak by transferring this excess fluid back into the central circulation.

11. This animation illustrates how peripherally acting pulmonary agents attack and damage the thin alveolar-capillary membrane, increasing the leak of fluid into the interstitium. This excess leak eventually overwhelms the capacity of the lymph system to return fluid to the circulation. Accumulation of fluid in the interstitium causes the lung to become stiff. The casualty interprets this decreasing pulmonary compliance as chest tightness and shortness of breath. In the later stages of injury, the alveolar epithelium is also damaged and protein-rich fluid leaks into the alveoli, destroying the surfactant layer and severely restricting gas exchange. Frank pulmonary edema results with frothy, pink sputum, hypoxia and respiratory failure.

12. CLINICAL CONSIDERATIONS
Peripheral agents cause pulmonary edema
damage alveolar-capillary membrane
Latent period
symptom onset may be delayed hours to days
Dyspnea
objective signs appear later than symptoms
Crackles
Hyposemia
Frothy Sputum
Sudden death may occur
laryngeal obstruction (edema/spasm)
bronchospasm
Once the alveolar-capillary membrane is damaged and fluid begins to leak into the interstitial tissues of the lung, it may take hours before the normal compensatory mechanism is overwhelmed, pulmonary compliance decreases, and the casualty begins to complain of shortness of breath. This characteristic delay in the onset of symptoms is described as the latent period. Depending on the agent and intensity of exposure, there may be a latent period of a few hours to several days. There is also normally a further delay between the onset of symptoms and the appearance of objective clinical signs.
While a latent period is typical, severe exposure can also produce central airways symptoms like laryngospasm or bronchospasm that could become rapidly fatal.

13. CLINICAL CONSIDERATIONS
Infectious Bronchitis / Pneumonitis common
3-5 days post-exposure
fever,  WBC, infiltrates NOT always infection
prophylactic antibiotics NOT indicated
Effects exacerbated by exertion
compensatory mechanisms overwhelmed
strict rest, even if asymptomatic
No specific therapy exists
As many as half the casualties of a pulmonary agent will develop a bacterial superinfection on the third to fifth day after the exposure. However, the routine use of prophylactic antibiotics is not indicated in this setting. Prophylactic antibiotic simply encourage growth of the most resistant organism already colonizing the respiratory tract, making subsequent treatment more difficult.
Complicating the issue is the fact that elevated temperature and elevated white blood cell count, and infiltrates on chest x-ray are typical responses to any toxic pulmonary exposure and do not generally indicate the presence of infection in the first three days.
In casualties allowed to exercise after their exposure, symptoms occur more rapidly, and are more severe, and outcome is worsened.
No antidotes or prophylactic agents exist for the effects of these toxic compounds. Standard techniques for the treatment of pulmonary edema are used.

14. CHLORINE - Civilian Uses
Chlorinated lime (bleaching powder)
Water purification
Disinfection
Synthesis of other compounds
synthetic rubber
plastics
chlorinated hydrocarbons
We are all familiar with many of the uses of chlorine and we recognize its irritating effects on skin and mucous membranes from our contact with chlorine as a disinfectant and water purifying agent. Chlorine is also used extensively in the chemical industry as a precursor or building block compound for the chlorinated- hydrocarbon plastics we use everyday.

15. CHLORINE - Physical Properties
gas at STP (bp = -34° C)
2.5 times heavier than air
green-yellow color
acrid, pungent odor
Chlorine is a true gas at standard temperature and pressure. Because chlorine was the first effective chemical warfare agent, the term poison gas became linked with any chemical agent used on the battlefield, even though most other agents are volatile liquids rather than gases. Chlorine is heavier than air, so it tends to hug the ground and settle in low areas such as trenches. A chlorine cloud has a greenish, yellow color and we all recognize its acrid, pungent odor from contacts with the chlorine bleach used in swimming pools and washing machines.

16. CHLORINE - Tissue Effects
Effects are local not systemic
In central airways - from HCl
necrosis, sloughing
In peripheral airways
oxygen free radicals
react with sulfhydryl groups, disulfide bonds
damage alveolar-capillary membrane
The toxic effects of all the agents discussed in this lecture, including chlorine, are local rather than systemic. The agent damages only those tissues in the lung that it contacts directly. Latest theories suggest that chlorine takes part in two different chemical reactions at the tissue level that produce the clinical effects we see.
When chlorine comes into contact with the moist mucous membranes of the upper and central airways, the agent reacts with the water in these tissues to liberate hydrochloric acid. This hydrochloric acid is believed responsible for the characteristic central-airways effects caused by chlorine: irritation of the eyes, nose, and throat; coughing; choking; laryngospasm and bronchospasm.
In the peripheral airways a second chemical reaction occurs that generates oxygen free radicals. These free radicals attack the molecular constituents of the alveolar-capillary membrane, producing the increased leak that leads to pulmonary edema.

17. CHLORINE - Clinical Effects
Mild Exposure
suffocation, choking sensation
ocular, nasal irritation
chest tightness, cough
exertional dyspnea
Moderate Exposure
above sx + hoarseness, stridor
pulmonary edema within 2-4 hours
Even mild exposure to chlorine may produce a characteristic suffocating sensation. Because of chlorine’s intermediate characteristics, we see upper airway symptoms of nasal and ocular irritation and cough as well as peripheral symptoms of dyspnea and chest tightness.
Greater exposure produces more significant central symptoms like hoarseness and stridor, along with peripheral airways damage leading to pulmonary edema.

18. CHLORINE - Clinical Effects
Severe Exposure
severe dyspnea at rest
may cause pulmonary edema within min
copious upper airway secretions
sudden death may occur from laryngospasm
Development of pulmonary edema may be quite rapid following severe exposure to chlorine. The latent period between exposure and onset of symptoms may be as short as an hour or less. The central effects of a severe exposure may produce sudden death from laryngospasm or bronchospasm.

19. CHLORINE - Therapy Supportive care
oxygen
positive pressure ventilation
with PEEP to keep PaO2 > 60 torr
bronchodilators
Bacterial superinfection common (3-5 days out)
follow serial cultures
prophylactic antibiotics not indicated
No long-term sequelae (uncomplicated cases)
As chlorine produces the same non-cardiogenic pulmonary edema as phosgene, treatment is the same: bed rest, supplemental oxygen, and observation for at least six hours. If pulmonary edema ensues, intubation with positive pressure ventilation, PEEP if necessary, volume repletion, bronchodilators with or without steroids for bronchospasm, and antibiotics based on sputum surveillance and or identification of a causative organism.

20. CHLORINE EXPOSURE 36 y/o female 2 hrs post exposure resting dyspnea
diffuse crackles
PaO2 32 torr (room air)
CXR:
diffuse edema
w/o cardiomegaly
Here is a representative case of chlorine exposure. This 36 year-old, chemical industry worker was exposed to chlorine gas on the job. She presented to her local emergency room two hours later complaining of severe shortness of breath at rest. After only two hours, objective signs of exposure are already apparent. The physician notes diffuse crackles and rhonchi on auscultation. Room-air blood gas shows a partial pressure of arterial oxygen less than half the normal value. Chest x-ray suggests diffuse pulmonary edema without cardiomegaly. Following a short stay in the hospital on a ventilator, this patient recovered without sequelae.

21. PHOSGENE - Uses/Sources
Chemical industry
foam plastics (isocyanates)
herbicides, pesticides
dyes
Burning of:
plastics
carbon tetrachloride
methylene chloride (paint stripper)
degreasers
Phosgene is used extensively in the chemical industry as a precursor for chlorinated hydrocarbons like those found in plastics, herbicides and dyes. The facility in the photo is the Union Carbide plant in Bhopal, India. This plant was producing these types of compounds when, in 1984, a single release of methylisocyanate and phosgene killed thousands. Its sister facility in Chemical, West Virginia produces these same compounds.
When chlorinated hydrocarbon compounds like paint strippers and degreasers are burned, phosgene is one of the products of combustion. Because many tons of phosgene and related chemicals are used, stored and transported in this country daily, soldiers are probably at greater risk for exposure from peacetime release or fires, than from exposure by enemy action in war.

22. PHOSGENE - Physical Properties
Gas at STP (bp = – 7°C)
Cl 3.4 X heavier than air
colorless
C = O
Cl Carbonyl Chloride
Also known as carbonyl chloride, phosgene is a simple molecule, but its chlorine atoms are of great value to the modern chemical industry. Like chlorine, it is a true gas at standard temperature and pressure and is also heavier than air, so it may linger in low lying areas. It is a colorless compound. Pictured is a World War I poster displayed in barracks and mess halls to warn the troops that phosgene has the odor of green corn. The odor has also been described as fresh-cut grass, or new mown hay. Unfortunately, because phosgene has such minimal irritating qualities, by the time the odor is identified, the toxic limit may have been exceeded.

23. PHOSGENE - Mechanism of Injury
Reaction 1: hydrolysis, generation of HCl
CG + H2O CO2 + 2HCl -central effect
-laryngospasm
Reaction 2: acylation, X = NH, NR, O, S
CG + X COX2 + 2HCl -peripheral effect
-edema
Researchers theorize that, like chlorine, phosgene reacts with the tissues in two different ways to produce the clinical effects we see. Liberation of hydrochloric acid on contact with moist mucous membranes produces the central airways effects seen with large exposures. An acylation reaction occurs between phosgene and the molecular constituents of the alveolar-capillary membrane to produce pulmonary edema.

24. PHOSGENE - Clinical Effects
Mild Exposure
mild cough
dyspnea
chest tightness
Moderate Exposure
above symptoms plus
ocular irritation, lacrimation
smoking tobacco produces bad taste
Exposure to phosgene may cause only a vague complaint of chest tightness or shortness of breath at first. These vague complaints may be the only indication of exposure initially as the objective signs of injury are often further delayed.

25. PHOSGENE - Clinical Effects
Severe Exposure
severe cough, dyspnea
onset of pulmonary edema within 4 hours
may produce laryngospasm
Latent Period
s/s onset more rapid with higher exposures
Exacerbated by exercise
Even with severe exposure, there may be a latent period of several hours preceding the onset of pulmonary edema. In general, the shorter the latent period, the more severe the exposure. This situation leads to what we call our “Four-hour Rule”: As a rule-of-thumb, onset of pulmonary symptoms within four hours of exposure to any of the peripherally acting agents indicates that the exposure is severe and potentially fatal.
An important empirical finding from the First World War was that an otherwise survivable exposure sometimes became fatal if the casualty participated in some physical exertion after the exposure.

26. PHOSGENE - Therapy Supportive care
strict bed rest
maintain PaO2 with O2, PPV, PEEP
replete intravascular volume
bronchodilators for bronchospasm
surveillance cultures
antibiotics when indicated
No long-term sequelae (uncomplicated)
The goal of therapy for non-cardiogenic pulmonary edema is to support the patient’s vital signs long enough for the damaged alveolar-capillary membrane to heal. Initial treatment includes bed rest, supplemental oxygen and observation for at least 6 hours. If pulmonary edema progresses and alveoli fill with fluid, intubation and positive-pressure ventilation may be necessary to maintain adequate gas exchange. The addition of positive end-expiratory pressure (PEEP) will keep these alveoli open throughout the respiratory cycle and help maintain an adequate partial pressure of oxygen in the arterial blood.
Fluid shifting into the pulmonary interestitium and alveoli will significantly deplete the intravascular volume of these casualties. Unlike the patient with cardiogenic pulmonary edema, the phosgene casualty will require repletion of intravascular volume to maintain hemodynamic stability.
For those patients with pre-existing hyperreactive airways, bronchodilators with or without steroids may be useful to manage bronchospasm. It is important to note, however, that steroid use has not been shown to improve the outcome in those cases without superimposed bronchoconstriction.
Prophylactic antibiotics are not indicated for chlorine exposure. For bacterial pnuemonitis, antibiotics should be used when a causative organism has been identified, or when objective signs of infection are present after day three. Uncomplicated cases of chlorine exposure typically recover within 36 to 72 hours, generally without long term sequelae.
Portable ventilators, like the one pictured, capable of providing the high inspiratory pressures required for casualties with stiff lungs can now be found at some far-forward medical units. Definitive care of these casualties will still require their timely evacuation to the intensive care units found at the third or fourth echelon.

27. PHOSGENE - Case 1 40 y/o male 2 hrs post exposure mild dyspnea
normal physical exam
PaO2 88 torr (room air)
CXR: normal
This 40 year old chemical industry worker was exposed to phosgene on the job. He reported to the emergency room two hours after the exposure with complaint of mild shortness of breath at rest. On exam, however, the physician found no objective signs of injury and sent him home.

28. PHOSGENE - Case 1 7 hrs post exposure mod. dyspnea at rest
few crackles
PaO2 64 torr (room air)
CXR: mild interstitial edema
survived w/o sequelae
This same patient returned to the emergency room, however, five hours later with worsening dyspnea. Only at this point, seven hours after the exposure, were clinical signs of pulmonary edema evident. This patient survived his exposure without sequelae.

29. PHOSGENE - Case 2 42 y/o female 2 hrs post exposure
rapidly inc. dyspnea
PaO2 40 torr (room air)
CXR: infiltrates -
perihilar
fluffy
diffuse interstitial
death 6 hrs post exp.
This chemical worker was less fortunate. Her exposure was so severe that both symptoms and signs of pulmonary edema, including hypoxemia and visible infiltrates on chest x-ray, were apparent within two hours of this fatal event.

30. PFIB Organofluoride Polymers Toxic Combustion By-Products
polytetrafluoroethylene (“Teflon”)
many commercial uses
used in armored vehicles, aircraft
Toxic Combustion By-Products
perfluoroisobutylene (PFIB)
pulmonary edema similar to phosgene
Organofluoride polymers are valued by the chemical industry for their desirable chemical and physical properties. Polytetrafluroethylene (“Teflon”), for example, is valued by consumers for its slipperiness, because it prevents food from sticking to the pan. These polymers are used extensively in military aircraft and vehicles for their other characteristics, such as their lubricating and insulating properties.
When organofluoride polymers are burned, one combustion by-product is perfluoroisobutylene (PFIB). Inhalation of this toxic combustion product produces the same effect on the peripheral airways as phosgene.

31. PFIB - Clinical Effects
Teflon Pyrolysis at >800° C
liberates PFIB
10X more toxic than phosgene
latent period of 1-4 hours
followed by increasing dyspnea
s/s of pulmonary edema
usually recover within 72 hours, w/o sequelae
PFIB is liberated when these organofluoride polymers are burned at very high temperatures, like the temperatures that might be found in a tank or helicopter fire. PFIB produces the same type of pulmonary edema as phosgene, but is 10 times more toxic than phosgene. The latent period following PFIB exposure is typically shorter than the latent period following phosgene exposure. Symptoms may occur in one to four hours, rather than the one to 24 hours associated with phosgene inhalation.

32. PFIB - Therapy Supportive Care similar to treatment of phosgene rest
observation
O2, PPV with PEEP
Treatment of the pulmonary edema produced by PFIB exposure follows the same principles as treatment of phosgene exposure. Just as with phosgene inhalation, exercise post-exposure exacerbates the symptoms and worsens the outcome. The patient with PFIB exposure should be placed at rest and observed for at least 6 hours. Maintenance of adequate oxygenation in the face of pulmonary edema will likely require positive-pressure ventilation with PEEP.

33. HC SMOKE Obscurant smoke Zinc Oxide + Hexachloroethane
Combustion Products:
zinc chloride
phosgene chlorine
carbon tetrachloride hydrogen chloride
ethyl tetrachloride carbon monoxide
hexachloroethane hexachlorobenzene
Most service members have been exposed at some point to this next substance. HC smoke is the military’s standard, white obscurant smoke disbursed in grenades and artillery rounds. This compound is a fifty-fifty mixture of zinc oxide and hexachloroethane. This compound must be burned to generate white smoke. The products of this combustion process include a long list of potentially toxic compounds. Zinc chloride is the combustion product believed most responsible for the toxic effects of HC smoke exposure, the same type of pulmonary edema produced by the other peripherally acting agents.
The photo shows an armored vehicle generating fog-oil smoke. This type of smoke looks and acts like HC smoke, but does not liberate the same toxic by-products.

34. HC SMOKE - Clinical Effects
Mild Exposure
dyspnea
lab findings normal (monitor x 4-6 hours)
Moderate Exposure
initial severe dyspnea, resolves spontaneously in 4-6 hrs
return of symptoms within hours
CXR initially clear, later - dense infiltrates
hypoxia
bronchopnuemonia may lead to interstitial fibrosis
The clinical effects of HC smoke exposure are similar to those of phosgene exposure. Some differences are apparent. Complaint of dyspnea may occur early and resolve spontaneously. Shortness of breath may then recur after a latent period of 24 to 36 hours. While uncomplicated phosgene exposure rarely produces chronic changes in the lung, HC smoke inhalation can lead to interstitial fibrosis.

35. HC SMOKE - Clinical Effects
Severe Exposure
rapid onset, severe dyspnea
paroxymal cough with bloody sputum
hemorrhagic ulceration of upper airway
rapid onset pulmonary edema
may have rapid onset laryngeal edema/spasm, death
Unlike phosgene, severe exposure to HC smoke typically produces hemorrhagic ulceration of the upper airway as well as pulmonary edema. The potential also exists for sudden death due to laryngospasm.

36. HC SMOKE - Therapy Supportive care of:
acute tracheobronchitis
pulmonary edema
Steroids probably useful (acutely)
inflammatory fibrotic changes
long-term PFT follow-up
10-20% develop interstitial fibrotic changes
Treatment of pulmonary edema from HC smoke is generally the same as therapy after phosgene inhalation. One important difference is the potential benefit of steroid use acutely to reduce the incidence of interstitial fibrosis. These patients will also require long term follow-up to monitor for these fibrotic changes.

37. HC SMOKE EXPOSURE 60 y/o male 8 hrs post exposure mod. severe dyspnea
diffuse crackles
PaO2 41 torr (room air)
CXR: dense peripheral infiltrates
In this representative case, a 60 year old sailor inhaled HC smoke in an enclosed space. Eight hours post-exposure he complained of severe shortness of breath. Signs included diffuse, coarse crackles on auscultation, arterial PO2 of 41 torr, and diffuse, dense peripheral infiltrates on chest x-ray. He subsequently recovered and was discharged from the hospital.

38. HC SMOKE EXPOSURE 3.5 months later
persistent, moderate dyspnea at rest
PaO2 = 61 mmHg (room air)
biopsy: diffuse interstitial fibrosis
This same patient returned three and a half months later with complaint of persistent resting dyspnea. Open lung biopsy revealed diffuse interstitial fibrosis. Steroids had not been used in the initial therapy.

39. NITROGEN OXIDES Nitrogen Dioxide (NO2, N2O4) high temp combustion
arc welding
nitrate-based explosives
enclosed spaces
diesel engine exhaust
All of us have been exposed to oxides of nitrogen. Nitrogen dioxide is the component of photochemical smog that gives smog its reddish-brown color. Exposure to high levels of nitrogen oxides, particularly in enclosed spaces, can produce peripheral airways injury leading to pulmonary edema. Service members may contact these compounds in several ways. Nitrogen dioxide is produced by high-temperature welding or burning processes. Discharge of the nitrate-based explosives found in small arms rounds, artillery shells, and other military explosives produces nitrogen dioxide. Even diesel engine exhaust contains substantial quantities of nitrogen dioxide.

40. NOx - Clinical Effects Symptoms similar to HC exposure
may remit spontaneously
exacerbated by exertion
Long Latent Period
may be asymptomatic for 2-5 weeks
Fibrotic changes may occur
PFTs may show chronic airway obstruction
Like HC smoke, exposure to oxides of nitrogen may produce dyspnea that remits spontaneously, then recurs following an extended latent period. In this case, dyspnea may return following a relatively asymptomatic period lasting for several weeks. Exposure to oxides of nitrogen is also associated with long term fibrotic changes in the lung.

41. NITROGEN OXIDES - Therapy
Supportive Care similar to HC exposure
rest
observation
O2, PPV with PEEP
steroids
Treatment of nitrogen dioxide exposure is similar to treatment of HC smoke exposure. Standard therapy for pulmonary edema may be supplemented with acute steroid therapy to minimize fibrotic changes that lead to persistent airways obstruction.

42. SUMMARY Inhaled toxic agent effects may be
Central, peripheral, or combined
Latent period - “dose” dependent
Onset of effect
Symptoms occur before signs
< 4 hours - severe, often lethal exposure
> 4 hours - lethality less likely
Mild to moderate exposures to toxic pulmonary agents produce characteristic effects associated with their solubility and reactivity. Highly soluble or reactive agents like mustard cause obstructive problems in the central airways, while less soluble compounds like phosgene attack the peripheral airways to produce pulmonary edema.
In general, the shorter the latent period between exposure and symptom onset, the more severe the exposure. Pulmonary symptoms occurring within four hours of exposure indicate a potentially fatal outcome.

43. SUMMARY - Therapy Terminate exposure Resuscitate - ABCs
Maintain strict bed rest
Observe for 6 hours
If abnormal, assess for additional 24 to 36 hrs
provide supportive care
Casualties presenting with a history of exposure to some toxic pulmonary agent should be placed at bed rest and observed for at least six hours. If the casualty exhibits any symptoms during that time, appropriate supportive care should be provided to maintain adequate oxygenation and ventilation.