Medical Aspects of Chemical Warfare (2008) - The Black Vault

Toxic Inhalational Injury and Toxic Industrial Chemicalscal activity. This same response mechanism has beendemonstrated in smokers. 66 It is well established thatthe toxic effect of smoking is largely a free radicalmediatedprocess.SPECIFIC INHALED TOXIC-GAS–INDUCED EFFECTS AND THEIR TREATMENTSDefining treatment strategies and clinical medicalmanagement for toxic gas exposure is problematic.In most cases the chemical inhalant is unknown. Inother cases there may be multiple chemical exposure,patients may be too confused to accurately recall theduration of inhalation, and the patient’s health andage may affect the outcome. Many chemicals can causehyposmia or even anosmia following inhalation, makingthe assessment of duration and type of chemicalagent inhaled all the more difficult. Some individualsare known to be much more chemically sensitized thanothers, especially if, for example, asthma, smoking, oran acquired sensitivity is present. Many of the chemicalsdiscussed thus far are listed as causing RADS oroccupationally-induced asthma. 67,68 Currently, mostdoctrines describe management, including ventilationsupport, pulmonary function tests, chest radiographs,supportive fluid replacement, and antiinflammatorytreatment. The mechanisms of toxicity in acute lunginjury processes are largely consistent from chemicalto chemical, and injuries detected early will respondmore readily to supportive or specialized treatment.Several compounds for which experimental or evenclinical supportive therapy has been successfully usedare detailed below.AmmoniaInhalation exposure to ammonia, generally considereda central airway compartment irritant, can causedamage to the airway epithelium and the alveolarcapillarymembrane. Acute signs and symptoms ofinhalation, typical of irritant gases, include coughing,bronchospasm, difficulty in breathing, pulmonaryedema, hypoxemia, and respiratory failure. 69 At death,hemorrhagic pulmonary edema can be a hallmark ofexposure. Interstitial fibrosis has been observed in patientsfollowing accidental exposure to ammonia. 70In rabbits exposed to nebulized ammonia at anestimated accidental exposure level (35,000–39,000ppm over 4 minutes), acute and severe lung injuryoccurred. Decreased Pao 2and increases in airwaypressure and Pac o 2were evident from 1 to 6 hoursafter exposure. 69 In this experimental model, the useof inhaled corticosteroids such as budesonide administered30 minutes after exposure was not effective inimproving gas exchange or reducing elevated airwaypressure. Corticosteroids are controversial for therapyfollowing ammonia inhalation and ingestion exposurein humans.ChlorineAffecting both the central and peripheral airwaycompartments, chlorine inhalation leads to abruptbronchoconstriction, increased airway resistance,and decreased compliance. In humans who have diedfrom chlorine poisoning, severe pulmonary edema,pneumonia, and ulcerative tracheobronchitis havebeen seen. 71 Recently, epithelial cell necrosis, smallairway dilation, and microvascular permeability havebeen found. 44 Efficacious therapeutic treatments havebeen tested in experimental models using large swine.Aerosolized terbutaline or the corticosteroid budesonidereduced acute lung injury when administered30 minutes after a 400 ppm × 20-minute exposure. 72Lung function was improved even more when bothcompounds were administered in combination. Theeffect of terbutaline or budesonide corroborates thebiochemical response mentioned earlier: terbutalinehelps increase cAMP levels through the stimulationof β-adrenergic signaling pathways and adenylate cyclase,thereby increasing tight junction strength and theintegrity of the air–blood barrier, which reduces fluidtransport through compromised basement membranes.Budesonide can work by reducing proinflammatorycytokines and by stabilizing membranes by limitingthe effects of membrane lipid peroxidative processesand the subsequent release of reactive mediators.Hydrogen CyanideAs a metabolic poison, HCN presents a challenge foreffective postexposure treatment. It is also considered tobe a cardiotoxin. Acute exposure to HCN rarely causesspecific changes in histopathological or pathologicalchanges. 73 Many people believe that the slightestcontact with HCN means instant death, but studies ofexperimental animals have disproven this belief. Sublethalconcentrations can produce incapacitation, withdizziness and nausea reported in some exposed people.74 However, treatment should always be provided asrapidly as possible. Supportive and antidote treatmentsagainst HCN include the use of sodium thiosulfate,which hastens the detoxification of CN; sodium nitrite,a methemoglobin former; and rhodanese, an enzyme353