Mustard Gas

MUSTARD GAS, beta,beta'-dichlorodiethyl sulfide (thiodiglycol chloride) /CH₂-CH₂Cl \CH₂-CH₂Cl. First obtained by Despretz in 1822. The physiological action of mustard gas on the skin was described by Guthrie. Its properties were studied in detail by Viktor Meyer together with N. Zelinsky in 1886. It was first used as a chemical warfare agent by the Germans on July 12-13, 1917, near Ypres, from which it received its name. Purified mustard gas is a pale yellow, transparent liquid boiling at 216-217°, freezing at +13.9° (technical grade at a temperature from +9° to +10°). Pure mustard gas has a faint odor. The technical grade used in warfare, not completely purified from sulfur compounds, has a dark, brown, or black color and possesses the smell of mustard, hence the name "mustard gas". It is sparingly soluble in water (less than 0.1%), and readily soluble in alcohol and chloroform. Upon heating, it decomposes immediately, releasing hydrogen chloride and toxic compounds that irritate the eyes, which have not been precisely determined. Water causes the hydrolysis of mustard gas with the formation of hydrogen chloride, but more slowly than phosgene, diphosgene, and lewisite, according to the formula: (ClCH₂CH₂)₂S + 2H₂O = (HOCH₂CH₂)₂S + 2HCl. It reacts very energetically with hypochlorites: Ca(OCl)₂ + 2(ClCH₂CH₂)₂S = 2(ClCH₂CH₂)₂SO + CaCl₂ with significant heat release and the formation of dichlorodiethyl sulfoxide, which is less toxic than mustard gas. Mustard gas is poorly volatile; at 15°, 1 m² saturates 0.4 g of mustard gas. However, its toxicity is so great that poisoning occurs even at these low concentrations. Due to the fact that mustard gas has a cumulative property, poisoning during a sufficiently prolonged stay in a contaminated area can occur even at concentrations that do not cause direct irritation of mucous membranes and are not perceived by smell, as a result of which poisoning can happen unnoticed by the victim. Physiological action. General characteristics. Mustard gas in both liquid drop and vapor states damages the skin and mucous membranes with which it comes into direct contact. Along with this local action, a resorptive action through the blood can also be assumed, since, firstly, mustard gas is highly soluble in lipoids and therefore rapidly absorbed by the skin and mucous membranes, and secondly, the decomposition of mustard gas in the blood occurs relatively slowly. However, experiments on poisoning animals by placing them for a certain period in a contaminated atmosphere, on the one hand, and experiments on introducing mustard gas into the blood or under the skin of animals, on the other, have shown that with the first method of poisoning, a lethal outcome requires the animal to absorb much smaller quantities via respiration (approximately 25 times) than is necessary for the same effect upon intravenous or subcutaneous administration of the poison. A characteristic feature of mustard gas poisoning is the latent period of poisoning, similar to that observed upon exposure to light, X-rays, etc. The duration of the latent period is shorter the more severe the poisoning. The entire process of mustard gas poisoning, and especially the healing of affected tissues, proceeds relatively slowly. Fatal outcome in the first days is rare. In severe poisonings, death occurs on the 3rd to 4th day, in lighter ones - after a week or later (up to a month). In cases of these late deaths, secondary infection plays a decisive role. The intensity of the lesion depends on the concentration (resp. dose), time spent in the contaminated atmosphere, and individual sensitivity. According to what has been said, the deepest lesions are usually caused by liquid mustard gas or mist, although if the concentration of gaseous mustard gas is maximal and the exposure is sufficiently prolonged, the lesions can also be very intense. According to their intensity, mustard gas lesions can be subdivided into: 1) mild - local phenomena of moderate strength (skin erythema, catarrhal lesions of mucous membranes), passing relatively quickly, favorable outcome; 2) moderate - local lesions are significant (blisters on the skin, purulent catarrh of mucous membranes), the outcome in various cases varies depending on the course of the poisoning; 3) severe - besides sharply expressed local phenomena, signs of general intoxication are present; in these cases, the outcome is definitely fatal. The phenomena of lesions of individual organ systems in various degrees of poisoning reduce to the following. Action on the skin. The latent period in moderate degrees is 4-6 hours. Upon the action of mustard gas per se on sensitive skin, this period can shorten to 1 hour, and with a weak concentration of the poison and poorly responsive skin, it can stretch up to 24 hours. High temperature (local hot bath before applying mustard gas) shortens the latent period and enhances the lesion, as Glebovich's studies have shown. The phenomena of the lesion initially manifest as a pale pink erythema. Upon pressure, the color disappears. Then the affected area swells slightly and acquires a more intense color with sharply outlined edges. Subjective sensations are mildly expressed; itching and pain upon pressure are sometimes observed. If the lesion is of a mild degree, the process regresses following the described symptoms. The affected area turns brown, with the coloring being brighter at the edges and paler in the center. After 10-14 days, everything returns to normal, but the affected area retains abnormal pigmentation for a long time. At stronger degrees, but still of a weak lesion not producing blisters, some skin atrophy and late-onset alopecia are observed if the affected area was covered with hair. At moderate and severe degrees of poisoning, erythema is replaced on the second day by blisters. First, on the erythematous area, starting from the periphery, pinhead-sized vesicles appear, which then merge, sometimes forming very extensive blisters containing amber-yellow fluid and surrounded by a bright red border. A day later, the blisters usually burst. The exposed bottom of the blister is covered with a yellowish-brown coating. In the absence of complications (secondary infection), a brown scab forms at the site of the blister after 2-3 days, falling off in about two weeks and leaving a hyperemic scar with brownish pigmentation. Histological examination of the skin reveals inflammatory phenomena expressed in hyperemia, hemorrhages, leukocytic infiltration, and tissue edema, with capillaries in the central part of the lesion possibly being contracted and containing less blood. For later periods, degenerative changes in tissues transitioning to necrosis are extremely characteristic. The latter penetrates deeply - down to the corium, which may also be partially necrotic. Blisters form as a consequence of the detachment of the epidermis by transudate from the necrotic papillary layer. Necrosis can also be observed in cases where the action of mustard gas was not energetic enough to form a blister. The necrotic nest is surrounded by a demarcation zone of hyperemia and leukocytic infiltrate. In experimental lesions of a rabbit's ear with a few drops of liquid mustard gas, necrosis spreads through the cartilage across the entire thickness of the ear, the result of which is a complete perforation of the ear. In the deeper layers of the corium, infiltration is less pronounced than in other layers, and it appears more strongly around hair follicles and sweat glands. Upon the action of mustard gas on the skin of animals, the same phenomena are discovered, but no blisters are observed due to the thinness of the stratum corneum, which bursts very quickly, and partly thanks to a greater connection by means of hairs between the superficial and deep layers of the skin. A peculiarity of the local action of mustard gas on the skin is that the size of the affected area grows. Thus, in experimental lesions, the diameter of the affected area turns out to be larger than the diameter of the spot smeared with mustard gas. This is explained by the ability of mustard gas to diffuse in lipoids. Not all areas of the skin are equally easily damaged by mustard gas. Most sensitive are areas with delicate skin (genitals, inner side of joint folds), as well as areas subject to friction (lower back, buttocks). Abrasions on the skin increase its susceptibility (Drugov). Skin that has already suffered from mustard gas is equally sensitive. Among people, there are subjects who are very sensitive, upon whom mustard gas acts in concentrations harmless to others, and conversely, there are people who are very resistant. The concentration of mustard gas needed to obtain a specific effect in the latter can be up to 40 times higher than in the former. Negroes are distinguished by significant resistance to mustard gas. Among animals, horses are especially sensitive to mustard gas, but like other animals, they do not form blisters; however, transudation occurs very energetically, which is why the affected area swells significantly. Action on the eyes. Direct irritation of the eyes by mustard gas at the very moment of its action is weakly expressed, and some irritation caused by concentrated vapors quickly passes after their cessation. The characteristic mustard gas lesion develops only after a latent period, which is however shorter here than for skin phenomena (on average 2-3 hours), and eye damage is usually the first among the symptoms of mustard gas poisoning.

Under the action of weak concentrations (latent period 6 hours), there is a sensation of a foreign body (sand), lacrimation, hyperemia of the conjunctiva, edema of the conjunctiva and eyelids. After a few days, everything passes. At higher concentrations, the latent period is shorter. Photophobia and blepharospasm are added to these symptoms. Red at first, the eyelids may become pale as a result of edema. On the 2nd–3rd day, conjunctivitis becomes purulent. On the surface of the eyelids, especially along the edges, necrotic areas appear. In severe lesions, the stuck-together eyelids represent purulent bags. Damage to the cornea leads to necrosis of the superficial layers of the epithelium and its opacification (at the 10th hour). Microscopic examination reveals cellular breakdown and vacuolization of cells in the vicinity of the area with shed epithelium. At the border of the sclera and cornea, there is an infiltrate. Eyelid edema reaches its maximum on the 2nd day. Its subsidence begins from the 36th hour. The entry of mustard gas into the eye in the form of drops causes necrotic damage to all tissues and panophthalmitis. It should be noted, however, that the severity of the initial symptoms in mustard gas eye lesions often does not correspond to the final outcome, which turns out to be more favorable than might be expected. Damage to the upper respiratory tract appears after eye damage approximately at the same time as skin damage. All parts of the respiratory tract suffer, starting from the oral and nasal cavities and ending with the pulmonary alveoli. The process begins in the upper tracts, where it is usually most pronounced. At first, the disease has a mucous-catarrhal character, and then becomes fibrinous-purulent with the formation of false membranes, and finally, in severe cases, can cause necrotization of the mucous membrane of the respiratory tract. In mild degrees of poisoning, a hoarse voice and a slight cough are observed. In moderate degrees, severe laryngitis, complete aphonia, a painful, barking cough appear. Sputum and nasal discharge soon (on the 2nd–3rd day) acquire a purulent character. Post-mortem anatomical examination reveals damage to all respiratory tracts, from the nasal and oral cavities to the alveoli, especially pronounced in the upper parts: the larynx, trachea, and large bronchi! It manifests itself in hyperemia, hemorrhages, tissue edema, their cellular infiltration, and necrosis of the mucosa, especially its epithelial layer. At the same time, the formation of false membranes consisting of rejected necrotic epithelium, leukocytes, and fibrin is characteristic. In the lungs, the lesion is a focal purulent bronchopneumonia, often with tissue necrosis. Edema in them is moderate, significantly weaker than with suffocating toxic agents, and more pronounced in severe degrees of poisoning. The false membranes mentioned above can partially or completely clog individual bronchi and lead to the formation of atelectatic and emphysematous foci. In particularly severe cases, necrosis of the lung tissue turns into gangrene. Secondary infection is of paramount importance in the entire course of the process, and thus is the cause of both the purulent and especially the gangrenous character of the process. The digestive organs suffer only in cases where food or drink contains mustard gas. At the same time, after the expiration of a latent period of 1–12 hours, symptoms of poisoning appear: salivation, vomiting, liquid purulent stools, sometimes discharge from the nose and mouth. At the same time, a depressed state and refusal of food and drink are observed. The lethal dose when administered per os is several milligrams per 1 kg of weight, i.e., significantly greater than the lethal dose by inhalation. Autopsy shows hyperemia, inflammation, and necrosis of the mucous membranes of the stomach and intestines. Their edema is weakly expressed at the same time. The resorptive effect, as indicated above, is much less pronounced than the local one and is practically significant only at high degrees of poisoning. It manifests itself in mental depression, although in severe cases, insomnia and phenomena of excitation are sometimes observed. Elevated temperature, vomiting, especially at first; constipation is usual. When mustard gas is experimentally administered into the blood of animals, respiratory excitation and loose stools are observed at the beginning of poisoning. After 2 hours, a drop in blood pressure occurs with symptoms of collapse and convulsions. Autopsy reveals hemorrhages in the lungs and inflammatory phenomena in the intestines. Examination of metabolism in those poisoned by mustard gas shows an increased excretion of nitrogen, ammonia, creatinine, and phosphoric acid, which indicates an increased breakdown of tissues. Changes in metabolism are very protracted and, in animal experiments, appear particularly sharply during their starvation. Theories of mustard gas poisoning. The local effect is explained differently by various authors. Marshall explains the local effect by the penetration of unhydrolyzed mustard gas inside the cells, where, thanks to hydrolysis, HCl is split off, which, by changing the concentration of hydrogen ions, is the cause of further degenerative processes. Flury and Wieland attribute the tissue-damaging action to oxidation products of mustard gas—sulfoxide and sulfones. Vedder suggests that the entire mustard gas molecule reacts with cell elements. Therapy of mustard gas lesions. First aid, apart from removal from the poisoned zone, which, in view of the persistence of mustard gas, is of particular importance, consists of washing the poisoned, cutting hair, and providing clean clothing. Footwear can be de-mustard-gassed with bleaching powder. Measures for the immediate removal or destruction of mustard gas already adsorbed by the skin are also advisable. For the purpose of removal, it is recommended to first remove drops of mustard gas with blotting paper and then apply washing the skin with various solvents, constantly changing the liquid, since the solvent that has captured mustard gas can itself become a source of damage to neighboring areas of the skin. According to Troitsky, rough friction should be avoided. Vedder especially recommends gasoline and kerosene for washing, giving preference to the latter, and advises washing the skin for 30 minutes. According to Troitsky's experiments, gasoline is better than kerosene and, applied 3–8 minutes after the application of mustard gas, can completely prevent skin damage; after 20–30 minutes, the latter can only be weakened. Washing should be carried out for 3–10 minutes. Soap alcohol gives approximately the same effect as gasoline (Serebrov). The best effect is given by carbon tetrachloride and amylene (Troitsky), surpassing both kerosene and gasoline. The disadvantages of amylene include an unpleasant odor and fire hazard. For the purpose of destroying mustard gas, the use of potassium permanganate and bleaching powder was proposed. According to Magnitsky's experiments, the results are worse than with solvents. Even a strong solution of potassium permanganate (1:100), applied after 1 minute, does not completely prevent skin damage. Bleaching powder also gives weak results, which, moreover, itself possesses irritating properties. The purpose of further therapeutic measures on the skin is: 1) to prevent complications (cave secondary infection!); 2) to sterilize dead skin elements; 3) to accelerate healing; 4) to reduce itching. For skin disinfection, a solution of potassium permanganate (1:1,000) is used. Protective dressings are indicated. Against itching—astringents, lubrication, and powdering. Upon the formation of a blister, it is recommended to open it to preserve the desquamated epithelium as a protection for the ulcer and apply an aseptic dressing. American authors highly recommend the use of Dakin's solution, as well as alternating the latter (1–2 hours) with the use of a hypertonic (2 hours) and physiological (1 hour) solution. The same authors recommend other preparations acting similarly to Dakin's solution by split-off chlorine, such as chloramines in the form of ointments. For wounds, other low-irritant disinfectants (rivanol, eucupine, and vuzine) are also recommended. To accelerate healing, an ointment with Scharlachrot (4–8%) is recommended. For the treatment of eyes, it is recommended to wash them with water, a 1% soda solution, a 1:10,000 potassium permanganate solution, cold compresses, saturated solutions of boric acid, weak solutions of Dakin and chloramine (for example, 0.5–0.1%). For photophobia—atropine. The use of cocaine is allowed with caution in view of the possibility of corneal ulceration. For corneal ulceration—lapis solution. Washing is desirable to do immediately. However, in practice it is hardly possible to start it quickly enough, and washing performed only 1 minute after the application of mustard gas has a relatively weak effect, only slightly slowing down the process (Zarubin). When the oral cavity, nose, and pharynx are affected, rinsing with weak soda solutions or non-irritating disinfectants (weak solutions of Dakin and chloramines) is suggested. When the larynx is affected—inhalations with menthol, Eucalyptus oil. For bronchial spasms—atropine and adrenaline. In view of the importance of secondary lung infections, special attention should be paid to the hygienic conditions of the patients. It is desirable to humidify the air of the wards. In bronchopneumonia—the usual use of expectorants, cardiacs, and oxygen. Protein therapy (administration of milk) has also been proposed for the purpose of rapid separation of false membranes.

It is necessary to bear in mind the slow course of the process and the prolonged metabolic disorder, as a result of which a prolonged stay in a sanatorium should be prescribed after recovery.