Page 107 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

74 SECTION | I General

VetBooks.ir hemoptysis are common initial signs following exposure prevented noncardiogenic pulmonary edema (Kennedy
Progressive dyspnea, productive cough, cyanosis, and
et al., 1989). N-acetylcysteine (Mucomyst) administered
intratracheally to rabbits 45 60 min after inhalational
(Wells, 1985; Borak and Diller, 2001). Hypoxemia and
hypoventilation are common secondary to respiratory dis- exposure to phosgene (1500 ppm/min) decreased pulmo-
tress (Wells, 1985). Animals may develop secondary GI, nary edema, production of leukotrienes, lipid peroxida-
hepatic, renal, or brain injury, due to lack of oxygenation. tion, and maintained normal glutathione levels as
In a dog model, severe phosgene poisoning caused initial compared to rabbits exposed to phosgene only (Sciuto
bradycardia followed by tachycardia and progressive et al., 1995). Other treatments, such as ibuprofen (Guo
hypotension (Patt et al., 1946). Cardiac failure may occur et al., 1990), supplemental oxygen, sodium bicarbonate,
secondary to severe pulmonary edema. and aerosolized surfactant (Mautone et al., 1985), or corti-
Direct contact with the liquefied material can cause costeroids, prostaglandin E1 and atropine (Chemstar,
dermal burns (Proctor and Hughes, 2004) and severe eye 1996), have been shown to have beneficial effects in
irritation, corneal opacification, and frostbite (Proctor and laboratory animals.
Hughes, 2004). Corneal opacification has also been pro-
duced in cats exposed to highly concentrated phosgene Concluding Remarks
gas (Grant and Schuman, 1993).
Prognosis is directly related to the extent of pulmonary Phosgene is heavier than air and will pool in low-lying
injury. If the animal survives 24 48 h, the prognosis areas. This heavy vapor density, 3.4 times that of air,
improves. Pulmonary edema begins to resolve after 2 3 made phosgene practical for trench warfare. Phosgene is
days. Survivors may have suppressed natural killer cell considered to be nonpersistent in the environment. Air
activity and are more susceptible to infectious agents. concentrations are reduced by atmospheric water, such as
Secondary infections may become evident 3 5 days after rain or fog (Borak and Diller, 2001). Rescuers should
exposure. They may also have persistent exertional dys- wear proper protective clothing when treating exposed
pnea, reduced exercise capacity and abnormal pulmonary patients. Fortunately, the potential for secondary contami-
function tests (Borak and Diller, 2001). nation of rescue personnel is low, as the gas does not per-
sist in fabric or leather. Phosgene is used extensively in
Treatment industry as a chemical precursor and this widespread
availability makes it an attractive agent for terrorist use.
If inhalation exposure occurs, remove animals to fresh air
(higher ground) and monitor for respiratory distress. MUSTARD GAS
Exposed skin should be washed with soap and water.
Exposed eyes should be flushed for 15 min with tepid Background
water. Asymptomatic animals should be monitored for
12 24 h for development of pulmonary edema (Borak Mustard gas (Agent H, C 4 H 8 C l2 S) is a vesicant agent used
and Diller, 2001). Symptomatic animals should receive in chemical warfare. It causes necrosis of the skin, eyes,
100% oxygen. If arterial blood gases or pO 2 continues to and respiratory tract. It is an organic lipophilic sulfide,
fall, intubation and ventilation is recommended. Plasma which is a bifunctional alkylating agent (Borak and Sidell,
phosgene levels are not clinically useful, and there is no 1992; Lewis, 2000). Mustard agent is a clear oily liquid in
specific antidotal agent. Management of patients with pul- its pure state. Due to impurities, however, it is normally
monary edema from phosgene is the same as for an ARDS amber to black, or yellow to brown in color (Munro et al.,
patient. Diuretics are not indicated and can worsen volume 1999; USACHPPM, 2001b; HSDB, 2005). The liquid
depletion. Mechanical ventilation with oxygen and posi- becomes aerosolized when dispersed by spraying or by
tive end-expiratory pressure is the mainstay of treatment. explosive blast from a shell or bomb (USACHPPM,
Intravenous fluids can help with cardiovascular sup- 2001a). Mustard gas has an odor resembling garlic, mus-
port, but monitoring closely for signs of volume overload tard, or horseradish. Systemic poisoning occurs more easily
is recommended. Colloids are preferred, as they will in warm climates than in temperate ones. Mustard gas is
remain in the vascular space for a longer period of time. still considered a major threat by the US military, as it is
Most arrhythmias will resolve with adequate oxygenation. easily manufactured and is both incapacitating and lethal.
The mechanisms underlying acute lung injury are not
well understood. Nebulized beta adrenergic agonists are Pharmacokinetics/Toxicokinetics
recommended if bronchospasm occurs. In a rabbit inhala-
tion study, animals exposed to toxic levels of phosgene Mustard gas is toxic by all routes of exposure (oral,
were dosed with intravenous aminophylline and subcuta- inhaled, dermal, and ocular) (EPA, 1985a; Sidell et al.,
neous terbutaline. If given within 10 min postexposure, it 1997; Lewis, 2000). Skin penetration of both the liquid