Farmer VIISYSTEMIC POISONS AND INCIDENTAL GASES

G • J • F ARMEN., M * D •

The group of chemical agents which I have been asked to discuss may be en-countered by the armed forces and also, under certain conditions, by ohe civilj-an

population/ Systemic poisons are breathed admixed with air, penetrate the epithe-lial lining of the lungs, pass into the blood stream and diffuse throughout theentire body. Any local action is either lacking or delayed ana 01 secondary im-portance .

This group includes carbon monoxide, nitric fumes, hydrocyanic acid, arsineand hydrogen sulphide. The first three agents are of most importance. Cyanogenchloride and cyanogen bromide are usually considered in this group, while dis-cussing hydrocyanic acid*

I. Carbon Monoxide. GO

Carbon monoxide is produced in any process where combustion of organicmatter occurs in the absence of an adequate amount oi air• It is a non-persistentgas and lighter than air. Military hazards include gun blasts,exhausts from motors of mechanized equipment, and stoves in augouts with inane-quate flues and ventilation, etc. The detonation of 1 kilogram of a modern highexplosive produces from 600 to 800 liters of CO. The atmosphere around a ouiSu-

ing shell may attain a concentration of 4.0 to 60 per cent of carbon monoxide.This may constitute a hazard to an unprotected inc.ivio.ual entering a confineo.space after an explosion. Little danger occurs in the open because of the light-ness and ready diffusibility of this gas.

fii civilian life the hazards are numerous. One has but to recall the recenttragic Cocoanut Grove Restaurant fire in Boston to realize the danger of beingtrapped in a burning building. In their report, of tnis oatastrophy , I axon andChurchill state (J.A.M.A. 120, 1385, 1942) "Some of the dead showed no burnsjthey had obviously been asphyxiated. Many showed the cherry-red color of carbonmonoxide poisoning. 11 Leaking ga,s mains, defective gas heating equipment, andimproperly installed stoves take a toll of many lives annually. The CO content ofilluminating gas ranges from 10 per cent in coal gas go 30 to 40 per cent inwater gas, °Stove cleaners in steel mills are subjected to CO poisoning unlessremoved to fresh air at frequent intervals.

Carbon monoxide is not directly tox5_c to the tissues. Its affinity xorhemoglobin is 210 times greater than that of oxygen^ for hemoglobin. Poisoning istherefore due to an induced anemic anoxia as shown in the following slides

MECHANISM OF CO POISONING

CO produces tissue anoxia1st". CO t hemoglobin t carboxyhemoglobin

CO r Hb v HbCO

Slide OCD 1HbCO unavailable for O2 transportAffinity CO for Hb is 210 X O2 f°r Hb.

Thus - if cone, of CO in inspired air isonly 1/210 that of 02 ,

the bloodwill contain equal amounts ofHbCO and Hb02.

Farmer VII

CALCULATIONS

The presence of carboxyhemoglobin alters the dissociation curve of oxyhemo-globin in an unfavorable manner so that less oxygen is given up in the tissues.For example, the patient with CO poisoning, sufficiently severe so that 60, per centof the normal hemoglobin content of his blood is inactivated, is considerably worseoff than the patient who lacks 60 per cent of his normal hemoglobin quota as aresult of anemia. Each has 4-0 per cent of hemoglobin for combination with butthe patient with circulating carboxyhemoglobin does not release but roughly asmuch oxygen in his tissues as the anomic patient. Such an individual is near thepoint of collapse, whereas, the anemic patient way show no marked symptoms.

The toxic effects of CO arc therefore purely secondary to the tissue anoxia.While it is true that under very high CO tensions, cellular respiratory enzymes maycombine with the gas, the concentrations capable of causing clinical poisoning aretoxic only, by virtue of the formation of carboxyhemoglobin. Cellular respirationwill continue in a normal manner if sufficient oxygen is supplied.

The symptoms of carbon monoxide poisoning require no discussion before thisaudience. The following slide correlates the blood saturation with subject'scondition.

SYMPTOMS OF CO POISONING

Air normally, 20,9$ Op by volumeTherefore, 0,1$ Cu by volumefurnishes CO cone, of 1/210 that of content.This is only 1 part in 1000 parts air.

Slide OCD 22nd, HbCO interferes with dissociation

of O2 from remaining Hb02 and thusstill further reduces amount ofavailable to the tissues.

Blood Sat*n, Symptom

0 - 10# None10 - 20% Tightness across forehead,

possibly headache0 20 - 30% Headache, throbbing temples

30 - L%0% Severe headache, weakness,Slide OCD 3 dizziness, dimness of

vision, nausea, vomiting-collapse.

oITNIo Above symptoms, collapse,syncope, increased pulseand respiration.

50 - 60% Syncope, increased respira-Slide OCD A tion and pulse, coma with

intermittent convulsions.60 - 10% Coma, intermittent convul-

sions, depressed heartaction and respiration,possible death.

Farmer VII

(x\fter Sayers and Davenport)

It is evident from the above that symptoms merge one with another, theseverity increasing as concentration increases. Exposure to high concentrations,causes a rapid saturation of the blood. The victim under these conditions mayexperience only transient weakness and vertigo before unconsciousness occurs,

Tho two important factors governing the toxicity of carbon monoxide, are theconcentration of gas in the inspired air, and tho duration of exposure.

These relationships are shown in the following tabic:

CARBON RONOXIDE POISONING

Henderson and Haggard (1927) formulated tho following simple rule forcalculating the probable toxicity of inhaled air of known carbon monoxide content:This rule states that the product of the Exposure time in hrs. X Parts Co in10,000 air.

If under 6, there is no danger to lifeIf product roaches 9, symptoms beginIf product reaches 1$, life is endangered.

The application of this formula indicates that a concentration of 0,1 volumeper cent (.10 parts per 10,000) of gas could be tolerated without symptoms for 30minutes, whereas a 90 minute exposure would be dangerous. The formula isapplicable only to normal persons at rest. Children are more suscoptable thanadults, because of their higher metabolic rates. Anemic individuals ore likewisemore susceptable. Small animals, as mice and birds, because of their highmetabolic rates, have been employed for the detection of toxic concentrations ofcarbon monoxide in mines, dugouts, etc. The air is safe for human beings as longas these animals remain unaffected.

70 - o0% Weak pulse, slowed respira-Slido OCD 5 tion, respiratory failure

and death.

Effect

Allowable for an exposure of

Air ContainsVol, %

several hoursCan bo inhaled for one hour

0,01

without appreciable effectCausing a just appreciable

effect after one hour 1 s

0,04-0,05

Slide OCD 6 exposureCausing unpleasant but not

dangerous symptoms after

0.06-0.07

one hour's exposureDangerous for exposure of

0,1 -0,12

one hourFatal in exposure of loss than

0,15-0,20

one hour

(Table after Jacobs)

0.4 and above

Farmer VII

The observed pathological changes are those resulting from anoxia. Cerebralcapillary damage resulting in cerebral edema and areelevated intracranialpressure. This damage may explain the severe headache following CO intoxication.Cellular changes may occur in the brain, and permanent damage to the centralnervous system result even if the victim recovers. The higher centers are moresensitive than the lower to oxygen deprivation. The heart and blood vessels mayalso be injured and cardiovascular as well as cerebral symptoms appear during thepost-exposure period. Small hemorrhages in the brain, heart, and other organs,with perivascular infiltration and focal necroses have been observed in bothexperimental and clinical CO poisoning. The blood has a characteristic cherry-rodcolor, duo to carboxyhcmoglobin.

The diagnosis of CO poisoning is often presumptive, from the circumstancesunder which the victim is found. The characteristic cherry-red cyanosis of theskin, mucous membrane and area under the fingernails, is pathognomic,

A simple method to establish the presence of CO in blood is the pyrotannicacid test. Normal blood when diluted with water and treated with a mixture ofpyrogallic and tannic acids, gives a brownish-gray coagulum, whereas, bloodcontaining CO gives a light carmine colored coagulum. The intensity of thecarmine color is proportional to the degree of CO saturation. For medico-legalpurposes carbosyhemoglobin should bo determined in blood by an accepted chemicalmethod.

Treatment of acute CO poisoning commences when the victim is removed from thecontaminated atmosphere and placed in air. Persons effecting the rescue shouldbo provided with an oxygen helmet or special canister, since the regular servicemask affords no protection. Tho entire plan of treatment is based upon thedissociation of carboxyhemoglobin and its replacement by oxyhemoglobin. Thefollowing outline is taken from notes of Prof, Louis Goodman of Yale University;

THERAPY OF CO POISONING

Ordinary service mask - No protectionObject of therapy - Got adequate

O2 to tissues

Slide OCD 7

1.2.3.

Remove victim to pure airArtificial respiration if necessaryAdminister pure O2 if available,

because;a) High C>2 tension hastens

dissociation of HbCO

Slide OCD 6 4.

b) High tension increasesamount of O2 dissolvedin plasma (from 0,3cc.to 2.2 cc. per 100 cc. Blood),and allovrs 15% more ©2 to becarried by blood

Better yet, administer 5%>to 10$ CO2 in oxygen.

a) CO2 stimulates respiration,thus hastens elimination of CO

b) CO decreases the pH of blood,thus Increasing the dissociation

Farmer VII

The use of CO2 and O2 permits the body to oxpell all CO in about 30minutes. The use of oxygon alone may require 30 to 90 minutes, and fresh airapproximately 2 hours.

Goodman gives the following statement relative to methylene-blue therapy*"The dye was employed in the belief that it could serve in the place of tissueoxidases, poisoned by carbon monoxide. However, there is no evidence thatmethylene blue can function in this manner, there is no proof that tissue oxidasesare in the least affected by carbon monoxide concentrations encountered inclinical poisoning, and even if the claims were true, the presence of Garboxy-hemoglobin would prevent the possibility of sufficient oxygen reaching the tissue.Methylene blue is not entirely innocuous and is capable of converting hemoglobinto methemoglobin. By using this irrational therapy one would only be complicat-ing one type of poisoning with another, and still further reduce the oxygon-carrying capacity of the blood. The sporadic clinical reports of success withmethylene blue probably represent cases which recovered in spite of harmfultherapy. H

In view of the possibility of after-effects of severe CO-poisoning theprognosis should bo guarded. If coma persists over an extended period, markedcerebral damage has probably occurred. Neurological and psychiatric disorders,tachycardia and dyspnea may continue for months.

II. Nitric Fumes (Nitrous Fumes)

Nitric fumes constitute both an industrial and a military hazard. Theyare produced in the pickling of metals, especially brass, the detonation ofcordite or other high explosives, in industrial nitration plants, and whenevernitric acid comes in contact with organic material.

Published data show the breaking of carboys and other containers of nitricacid, to be the most common cause of fatal nitrous fume poisoning. Spilled acidshould be washed away with large amounts of water, and never absorbed by sawdustor other organic material. Clean sand may be used as a cover if necessary.

One will recall the disastrous fire at the Cleveland Clinic some years- agoin which casualties resulted from the inhaling of fumes from burning X-Ray Films.

The group of nitrous fumes includes the following chemical agents;

NITROUS FUMES

of HbCO into Hb and 09,

Slido OCD 9 5. Give supportive therapy.Xoop patient warmPrevent exertion, to keep O2needs at minimum.

DO NOT USE METHYLENE BLUE - ITS USEIS IRRATIONAL

Nitrous oxide, NpO — — colorless anaestheticSlide OCD 10 Nitric oxide, NO •— colorless, toxic

Nitrogen dioxide, NOp —■ — reddish brown, toxicNitrogen tetroxidc, — •— a colorless liquid

polomer of NOp

Farmer VII

Nitrous fumes in the presence of moisture may also contain nitricand nitrous (HNOg) acids.

Nitrous oxide is a weak innocuous anaesthetic familiar to you all.

Nitric oxide does not exist as such in air, being converted to nitrogen dioxide,V/e are, therefore, concerned only with nitrogen dioxide (N0 o ) and its polomcr,nitrogen tetroxido (NgO,), The properties of nitrogen tetroxide arc shown in thefollowing table:

Properties of

Tho composition of nitrous vapor is controlled entirely by temperatureas shown in the next slide:

From this data it is evident that regardless of the molecular forminhaled, the vapors arc at once altered to correspond to the equilibrium forbody temperature. At 4-0°C, approximately 30% exists as NCL and 70% as *

Those in the presence of water form nitric and nitrous acins.

The toxicity of nitrogen dioxide for man is shown in the following tablej

TOXICITY OF NITROGEN DIOXIDE FOR MAN

(Lehmann and Hasegawa, 1913)

Colorless crystals at -9.3°CYellow liquid at (10.0Yellow-rod liquid at 15.0Darker yellow-rod liquid at 20.0Boils, brown fumes at 21.3Completely volatilized at 22.0

Slide OGD 11 Chocolate brown vapor at 40.0Black vapor at 140.0

Slide OCD 12

Composition of Nitrous VaporColor varies with temperatureTemperature determines ratio:

Temp. NOp4-0°c, 70$ 30%60°C. 50% 50%

135°C. 0% 100%

ConcentrationParts per million Symptoms

by volume(Self experiments of Hasegawa)

Slide OCD 1364 Moderate irritation of larynx, respiration

slightly increased and shallow.

100 Marked irritation of larynx, cough

Farmer VII

Few symptoms are evident at low concentrations. The maximum allowableconcentration is 37 to 39 parts per million of air. According to Goodman, themain effects observed below this critical concentration are those resultingfrom the absorption of sodium nitrite which is produced by the action of nitrousacid in the alkaline tissue fluids. Approximately 20 milligrams of NaN0u> may boformed in the lungs and absorbed during 1 hour's exposure to a maximum allowableconcentration of nitrous fumes. The symptoms observed, therefore, arecharacteristic of the nitrite ion, namely, hypotension, headache, giddiness.Some mothomoglobin formation occurs. Men frequently exposed to low concentra-tions of nitrous fumes, may acquire a tolerance to the nitrite ion. They arestill susceptible to the irritant effects of the acids on the respiratory tract.

Higher concentrations of nitrous fumes produce marIced local irritationof the broncho-respiratory tract. Pulmonary edema occurs, and local ulcerationof the bronchi or lungs may result from nitric acid.

Frequently, an asymptomatic interval of from 4. to lo hour’s may followinhalation of toxic concentrations of nitrous fumes. Slight irritation of theeyes, nose and pharynx arc noticeable. Symptoms similar to those of phosgenepoisoning may then appear.

Because of the asymptomatic period, the victim nay not realize that hehas boon seriously gassed and returns to work instead of remaining at rest andunder treatment. Rapid fatalities occur when the concentration of nitrous fumesapproximate 500 parts per million of air.

The diagnosis of rd.trous fume poisoning is based upon the history of theexposure, the irritation to oyes, noso and throat, the pungent odor, and withhigh concentrations, the discoloration of the mucous membranes.

Protection against nitrous fumes is afforded by the service canister.Therapy is symptomatic and similar to that for phosgene poisoning. The prog-nosis is not good once pulmonary edema has developed. Casualties usually diewithin 2J+ to hours, A fatal broncho-pneumonia nay complicate a case whichapparently is recovering from pulmonary edema. Convalescence is prolonged.

Victims exposed to nitrous fumes may also have been simultaneously ex-posed to other gases especially carbon monoxide. The thermal decomposition of100 grams of celluloid, for example, furnishes U to 7 liters CO and about thesame amount of nitrogen dioxide. Symptoms of carbon monoxide poisoning maytherefore dominate the clinical picture.

207 Very marked irritation of nosoand larynx, cough, increasednasal secretion and lacrimation

(Lehmann 1 s conclusions)

37 May be tolerated for severalhours by many persons

74 May be tolerated for jr hour

117-154 Dangerous with somewhat prolongedexposure

234-300 Rapidly increasing danger*

Farmer VII

III. Hydrocyanic Acid. '’Vinccnnito”

Poisoning by cyanide is usually due to hydrocyanic acid or its salt,potassium cyanide. Acids, as weak as carbonic will liberate HCN from its salts.For this reason, inhaling of air from a container partly filled with KCN, maycause an undesirable systemic reaction. All compounds which release the cyanideion, have the sane mechanism of systemic action, and the principles of treatmentare the same.

The military use of HCN has not as yet boon very extensive. During 1915,in World War I, the French filled shells with hydrocyanic and phosgene, buthesitated to authorize their use. These were, however, usod in the battle of theSomme, July 1, 1916. The Germans suffered byit slightly, since they had learnedof the contemplated use of HCN by the French a week before its introduction atthe front, and had equipped their troops with special mask filters containing 1

_

gram of pulverized silver oxide scattered through the potash layers. Thisafforded adequate protection.

Most civilian cases of cyanide poisoning are those with suicidal intent.Because of its rapidity of action, hydrocyanic acid has been adopted by severalstates for use in executing criminals.

Pure hydrocyanic acid is a colorless liquid. It boils at 26°C,,yielding a vapor which is 0,93 as heavy as air. It has a faint odor resemblingbittor almonds. The vapor is exceedingly volatile (673 mg, per liter at 20°C.jand persists in the open only a few minutes after release. Because of the rapiddiffusion of this gas, military use required its admixtures with stannic chlorideand arsenic trichloride. Chloroform is also added to prevent polymerization.

It cannot be denied that if cyanide can bo released in battle ineffective concentrations, (a condition which might bo realized in dugcuts, deeptrenches, aboard ships, and within tanks, etc.) it will produce toxic or lethaleffects with dramatic rapidity, (thereby avoiding the destruction of desirableequipment),

The cyanide ion acts on the respiratory ferments of the tissue colls,preventing them from taking up oxygon. Death is due to on histotoxic anoxia,which is an asphyxia, in the presence of normal amounts of oxygen. It isremincsccnt of the old adage - "Water, water everywhere, but not a drop todrink,"

With tissue utilization suspended, there is loss than the normaldifference between the oxygon content of arterial and venous blood. The car*bondioxide content, of venous blood, is likewise close to that of arterial blood.Cyanosis docs not appear until the beginning of respiratory failure.

It will be recalled that in very low concentrations, the cyanide ionacts upon the chemoroceptors of the carotid body, producing indirectly throughthe medulla an intense stimulation of respiration. This action is transciont incharacter•

In cyanide poisoning the colls of nervous tissue are early affectedbecause of their sensitivity to oxygon want.

The following material relative to cyanide toxicity and therapy istaken largely from Goodman.

Farmer VII

The cyanide ion is detoxified in the body by combination with sulfur toform non-toxic sodium thiocyanate which is excreted by the kidney* The abilityof the tissues to detoxify cyanide is definitely limited, When the ion reachesthe circulation more rapidly than it can be disposed of, cumulative poisoningquickly ensues, resulting in death. If air containing less than the criticalconcentration ol 0,03 nigra HGN per liter (3 parts per 100,000) is breathed, thedetoxification mechanism, by conversion to thiocyanate, is adequate. Above thecritical concentration, the rapidity of poisoning-, depends upon the concentra-tion inhaled and the time of exposure. The lethal concentration is

0,2 mgm, per liter for 10 minutes exposure,

and 0,15 mgm, per liter for 30 minutes exposure.

Injection of 50 mgm, under the skin is lethal.

The symptoms of cyanide poisoning depend in character and severity onthe concentration of the inhaled gas. With high concentrations, a few inhala-tions result in unconsciousness and death with a few minutes. With lowconcentrations, the symptoms develop more slowly. They include weakness,giddiness, hyperpnoa, headache, palpitation and nausea with salivation. Cyanosisand unconsciousness then ensue, and terminal asphyxial convulsions are common.

The therapy of cyanide poisoning must be heroic and given rapidly to beeffective, According to Goodman, the most recent and best treatment consists inthe intravenous use IN SEQUENCE of sodium nitrite and sodium thiosulfate. Thecyanide ion does not combine with hemoglobin, but does combine rapidly withmethemoglobin. This affords a means of quickly removing the highly toxic cyanideion from the circulation by converting it to cyanmethemoglobin which is non-ionized and non-toxic. The method employed to obtain a methemoglobin is the in-jection of The nitrite ion quickly converts .emoglobin to methemoglobin.The cyanide ion is slowly released from cyanmethemoglobin and is then convertedto the non-toxic thiocyanate. This last-named reaction is insured and perhapsaccelerated by the presence of injected thiosulphate.

The following tables taken from Goodman, summarize these points!

MECHANISM OF CYANIDE TOXICITY

CN poisons the respiratorymechanism of tissue cells

Slide OCD U by combining with iron-containing respiratoryferments�DEATH is due to tissueanoxia and failure of themedullary respiratory center,

RATIONALE OF THERAPY

N02 r . Hb —) METHb (Rapidlyformed)

Slide OCD 15 CM P METHb —) CYAItETHb(Non-ionizednon-toxic)

Farmer VII

THERAPY OF CYANIDE POISONING

Approximately 20 lethal doses of cyanide have been antidoted inexperimental animals by the treatment suggested above. Its comparison withother methods of treatment is given in the following table:

CYANMETHb —) CN (Slowdissoc.)

NaTHIOSULPHATS -f CN”— Na THIOCYANATENaCNS (Non-toxic)

Slide OCD 16

Remove patient to fresh air, DONOT ENTER GASSED AREA'WITHOUT AMASK. If heart beats, start in-travenous therapy.Step 1. Inhalation of amylnitrite (30 seconds out of each2 minutes) while 3% NaN02 solu-tion is being prepared. '“(Nitro-glycerine* is effective). In oralpoisoning, wash out stomach inthis interval.

Slide OCD 17

Step, 2, Inject intravenously10 cc, of 3p NaNOp solution(0.3 gm,) Take 3 or 4 minutesfor injection.Step 3. Inject 30 cc, of a50/b solution (23 gms.)Take 10 mins, for injection.Step 4. Watch patient closelyfor 24 to 48 hours.

Slide CCD 18

If symptoms recur, re-peat steps 2 and 3, usinghalf doses. If alarminghypotension occurs fromthe nitrite, epinephrineor ephedrine may be used.If anoxia from too muchmethemoglobin, inhalationof 100>2 oxygen may be nec-essary, or even bloodtransfusion.

Treatment No* M.L.D'sRequired tokill dog.

None 1Nitroglycerine 1

Slide Methylene blue 3OCD 19 Na thiosulphate 4

Na tetrathionate 4Amyl Nitrite 5Nail 0 2 5Methylene blue and Na tetrathionate 7

Farmer VII

If the patient survives an hour, recovery generally occurs. Aftereffects are rare. Mortality rate from acute cyanide poisoning is very high.

The isonitrites, cyanogen bromide and cyanogen chloride, produce thesystemic toxicity of cyanide and also act as lacrimators and pulmonary irritants.IV, Arsine Poisoning AsH^

Arsine is a colorless gas, heavier than air, inflammable, has agarlic-like odor and metallic taste. The last two properties are attributed toaccompanying impurities. Arsine is liberated with hydrogen when an acid acts ona metal, if either the acid or metal contain arsenic. The Marsh Test for arsenicis a familiar application of this principle. Arsine my bo liberated from in-dustrial wastes, as for example, wastes from chemical plants making sulphuric acidfrom arsenic containing pyrites.

Arsine has not as yet boon employed as a war gas. Storage battery gases,or waste tanks on ships, may theoretically constitute military hazards.

The extreme toxicity of arsine for man is shown in the following tabic:

Toxicity of For Man

The service canister affords adequate protection against arsine.

Arsine when inhaled, enters the blood and combines with hemoglobin.It is gradually changed to a toxic arsenical compound of unknown nature. It maybe an oxidation product. This toxic compound causes the hemolysis of the redblood corpuscles. Arsine has also a direct depressant action upon the centralnervous system.

The following table shows the rapid fall of erythrocytes in dogs gassedfor 30 minutes with a concentration of 0,53 mgm, arsine per liter of air.(53 parts in 100,000,000 air)

Amyl Nitriteand

Na thiosulphate 11NaNOp

and. uSlido OCD 20

Na tetrathionateNaNOp

and 21Na thiosulphate

Parts per100,000 air.

Time breathed Comment

250 30 minutes Fatal50 60 Dangerous30 Several hrs. Mild symptoms

Highly-concen-trated

Few whiffs Fatal

Farmer VII

BLOOD CHANGES FOLLOWING GASSINGT'lTH ARSINE

Hematin'ia appeared 6 hours after gassing and continued for4 days. Other symptoms include diarrhea, tarry stools, marked weakness anddepression. Eventually recovery was complete.

Pathological changes observed in arsine poisoning are mainlysecondary to the acute hemolytic crisis. Marked destruction of erythrocytes,enlargement of the spleen and liver and jaundice are present. Hemoglobin isprecipitated in the tubules of the kidney. The blood picture, urinary findingsand serum bilirubin arc the same as occur in any severe hemolytic anemia.

The symptoms of arsine poisoning depend in severity upon theconcentration of the gas and the duration of exposure. They may be delayed from6 to 36 hours following gassing.

Death may occur in severe poisoning before symptoms can appear,while mild cases may show only lassitude, headache, mild dyspnea, a rapid pulse,followed somewhat later by a slightly yellowish tinge to the skin. In the averagecase the outstanding symptoms are chills, fever, severe myalgia, nausea andvomiting, lumbar pain. The urine is scanty, deep-brown or rod in color, containsfree hemoglobin, bile pigments, rod cells, albumin and casts. Jaundice usuallydevelops on the second day. Aymptoms of anemia and anoxia arc present. Thepatient is weak and exhibits dyspnea*

Evidence of the depressant action of the gas on the central nervoussystem may be noted in the early phases of the poisoning. The blood picture istypical of an acute hemolytic crisis. Complete anuria with uremia may resultfrom the mechanical blockage of the renal tubules, by. the precipitation of freehemoglobin in that portion of the tubule where the urine becomes acid. The bloodcontains free hemoglobin, also mothomoglobin. A slatcy cyanosis may thereforeprecede the jaundice. The clinical laboratory findings are similar to those,observed in phonyIhydrazine poisoning, black-water fever, paroxysmal hemoglo-binuria, or acute hemolytic anemia from sulfonamides, etc. Death may occur bo-tween the third day and the end of the week.

In patients surviving the acute phases, subacute arsenical poisoning mayoccasionally be evident, particularly a peripheral neuritis. Other aspects ofsubacute arsenical poisoning are diarrhea, dermatitis, pigmentation, edemaespecially of the lower lids and ankles, and arsenical hepatitis and nephritis.

Erythrocytes Leucocytes

Before gassing 6,530,000 22,400Time of gassing 5,000,000 20,2006 hrs. after gassing 3,400,000 ) 12,0001st day 2,660,000) Hema- 23,2002nd day 2,450,000) turia 25,400

Slide OCD 21 3rd day 2,300,000) , 70,0004th day 2,260,000) 66,5005th day 2,570,000 54,000

10th day 3,750,000 15,60015th day 4,060,000 15,00024th day 5,010,000 14,000

Farmer VII

Recovery requires 4 to 6 weeks. Marked anemia and anuria arc gravesigns but victims may survive. About 30 per conu of the cases are fatal.

The main problem in diagnosis is the differentiation of arsine poisoningfrom other syndromes characteristic of acute hemolytic crisis. Tost the urinefor arsenic.

Treatment starts with the removal of the victim to fresh air. Therapy issymptomatic and designed to combat the anemia and impaired renal function. Ifanoxia is severe, oxygon inhalation may be indicated. Repeated blood transfusionsmay bo given. Ample fluids arc given in an attempt to promote diuresis. TheHRi 1!0

.

should be kfept alkaline to minimize the blocking of the kidney tubule byhemoglobin. Continue liberal amounts of alkalies until the urine no longer con-tains free hemoglobin.

Intravenous glucose, a carbohydrate rich diet, low in protoin and fat isadvisable if hepatitis is prominent. Iron salts and a nutritious diet aro givenduring convalescence to promote blood regeneration. The use of sodiumthiosulphate to promote excretion of arsenic is problematical.

V• Hydrogen Sulphide

Hydrogen sulphide, although briefly employed in World far I offers littleprospect of military importance during the present conflict. It has several un-desirable tactical features, and is easily detected by its characteristic odor,and readily absorbed by several typos of canisters.

Its properties are known to you all. It is highly toxic, a concentrationof 0,07 per cent (7 parts in 10,000) in inhaled air will cause death after anexposure of 30 minutes, Tho limit ox danger for prolonged exposure is said to bea concentration of $0 parts per million,

Tho gas is encountered in chemical laboratories, the manufacture ofsulphur dyes and of rayon, tho refining of petroleum, the manufacture of coal gas,and also in sower gas.

The symptoms of hydrogen sulphide poisoning other than those locallyproduced aro duo to the action of the gas upon tho central nervous system. Wheninhaled in low concentrations, the patient suffers from headache, nausea, dyspnea,vertigo and marked malaise, Higher concentrations first stimulate, then depresstho central nervous system. Stimulation may bo sufficient to cause hyperpnoaand convulsions. Eventually the respiration is depressed and death results fromrespiratory failure, with tho heart boat continuing for several minutes.

Hydrogen sulphide is converted by tho moist lung to sodium sulphide. Inthe blood stream this substance is oxidized to harmless sodium sulphate. Thisosidativo process is said to deprive the tissues of needed oxygen. This is saidto be the only mechanism by which tho gas can cause an anoxia. It is denied thatHpS reacts with hemoglobin forming sulfhcmoglobin. It has boon established thatHpS combines only with mcthomoglobin, which normally is not present in thecirculating blood, Methomoglobin is formed after death, and any formed fromputrfraction of tho intestinal contents will then combine to form sulfmethomo-globin. The bluish-green discoloration soon around tho intestinal vessels ofcadavers is formed in this way.

Farmer VII

Tho following tablo presents data on tho effects following inhalation ofair containing K2S,

SI'ISCTS OF HYDROGEN SULFIDE

An adjunct to the diagnosis of HoS poisoning is tho blackening of amoistonod silver coin or moistened load acetate paper by the victims breath.

Treatment commences with the removal of the victim to fresh air. If stillbreathing administration of and CCA is helpful. If respiration ceases, in-stitute artificial respiration using u2 and C02 as long as the heart continuesto boat.

If respiration and tissue oxygenation can be maintained the body oxidizesthe HoS to non-toxic Na2S0^.

Pneumonia nay follow in severe cases.

Acknowledgment:

In preparing this lecture extensive use has been made of tho materialprepared for a similar lecture by Dr. Louis Goodman of Yale University.

Acknowledgment is also made for material taken from the following sources;

Medical Aspects of Gas ■ arfaro Ireland, 1926War Gases — JacobsChemicals in T . r or-~ PrentissThe Toxicity and Potential Dangers of

Nitrous Fumes, Public Health Bulletin, No. 272Various other Government Publications.

Concentration of Air Effects

Partsi by volume Mg, per liter

1 in 2000 0.76 Very dangerous if inhaled for 15to 30 minutes. Causes severe

irritation of the eyes andrespiratory tract with risk ofpneumonia or serious injury tothe lungs, which nay readily

Slide OCD 22 prove fatal.

1 in 5000 0.304 Dangerous if inhaled for onehour. Causes severe .'Irrita-tion 0.1 the eyes and respira-tory tract. Eyes are affectedafter 6 to C minutes.

1 in 10,000 0.152 Symptoms of local irritationof eyes and respiratory tractafter one hour's exposure

Tabic from Jacobs "far Gases"