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SECTION I
GENERAL SURGERY
CHAPTER X
TETANUS
The incidence of tetanus in the American Expeditionary Forces was decidedly low; so low, indeed, as to warrant the statement that, as a disease, we had no real clinical experience with it: only 36 cases were reported as being associated with 176,132 battle injuries, or a rate of 0.014 per thousand.1 This fact in itself is worthy of more than passing notice and is but a further exemplification of our good fortune in being able to profit by the experiences of our Allies.
The relationship of soiled gunshot wounds and the occurrence of tetanus was well understood prior to the beginning of the war in 1914, and such injuries occurring on the highly fertilized ground of the battle fields of France were inevitably followed by a high incidence of tetanus. However, the Allies did not anticipate any such number of cases of tetanus as occurred in the first few months following the beginning of the war. Even had it been otherwise, there was neither organization nor adequate material for proper administration of antitoxin. Within a very few months, however, the British ordered that a preventive dose of antitetanic serum be given to every wounded man.2 The results of this order were reported to be excellent; in the latter half of the year 1915 only 36 cases of tetanus developed among those who received a preventive dose of antitetanic serum within 24 hours of receipt of injury.2 This measurable, though not entirely complete, control is graphically shown in Chart VI, which is a compilation of Maj. Gen. Sir David Bruce, chairman of the British war committee for the study of tetanus, to show the ratio per thousand among the cases of tetanus.3
The case incidence shown in Chart VI refers to cases of tetanus arising in hospitals in England among the wounded arriving there from the battle fields, and it does not have to do with the cases occurring in France; however, another study by Cummins4 which combined the incidence figures for the British Expeditionary Forces and those used by Bruce, shows a very similar curve.
The elevations in the incidence curve as shown in Chart VI may be ex-plained as being partly due to periodic, increased battle activities, and partly to the occurrence of trench foot. More especially is this true, in so far as trench foot is concerned, in 1916, to which further reference is made below. What is of greater interest, as regards the American Expeditionary Forces, is the almost uniform flattening of the curve during 1918, at a time when we were actively engaged with the enemy.
VARIETIES OF TETANUS BACILLUS
Tulloch, 5 by means of serological tests, identified four classes of tetanus bacilli. Twenty-three strains of the tetanus bacillus were obtained from war wounds of men not suffering from tetanus. Seventeen of these strains belonged
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to Type I, 3 to Type II, 2 to Type III, and 1 to Type IV. This relationship of type incidence did not obtain, however, in organisms from cases of tetanus: whereas 74 per cent of the tetanus bacilli obtained from nontetanus cases belonged to Type I, only 41 per cent of tetanus among the wounded could be attributed to Type I.3
CHART VI.-Incidence of cases of tetanus. Ratio of cases per thousand wounded, by months
PREVENTION
SERUM PROPHYLAXIS
Once the necessity for the administration of antitetanic serum to all injured men was fully appreciated, the belligerent nations so organized their medical forces as to insure the administration of the serum at the earliest possible moment following the injury. This meant the serum must be as readily available, and practically as far forward, as was the first-aid packet; some means of rapidly determining, by a mark-usually an iodine-painted cross on the forehand
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or by ticketing, whether or not an acutely injured man had received an adequate dose of the serum; and finally a checking up at the operating hospitals to insure protection in cases in which, through inadvertence, the administration of the serum had been omitted.
The British adopted 500 units as the preventive dose, to be given subcutaneously at a distance from the wound; the French, 10 c.c. (equivalent to about 600 units). 2
It was expected that this routine injection of serum would bring about the lowest possible incidence rate of tetanus; however, when, with the occurrence of large numbers of trench foot, it was observed that with such a condition tetanus frequently was associated, it was realized that the portal of entry into the body by the tetanus bacillus need not necessarily be an open wound.6 Therefore all cases of trench foot were included with battle injuries for which the serum was to be administered as a matter of routine, with the result that in trench foot the occurrence of tetanus was prevented.
It was appreciated by the British that 500 units of antitoxin was in many instances too small a dose, and on July 4, 1917, modified instructions required the use of 1,000 to 1,500 units "in all deep wounds in those which are contaminated with dirt, and in those in which there is fracture of bone." 3 The size of the dose, however, was not fully determined as late as December, 1918. Bruce at that time announced his preference for multiple and smaller doses,3 an attitude that was based upon the fact that the antitoxin disappears within the body within a relatively few days.
DURATION OF PASSIVE IMMUNITY
With the view of determining the duration of immunity conferred by antitetanic serum, MacConkey and Homer7 carried out a series of experiments on guinea pigs. In these experiments it was found that immunity from the minimum dose was considerably diminished at the end of 10 days, and at the end of 2 weeks it had about disappeared; immunity could not materially be prolonged without increasing the dosage of serum to a degree impractical in man. They concluded, therefore, that it is necessary, in order to maintain immunity, to repeat the usual protective doses about once a week during the danger period.
As stated above, the British, in 1917, required an increase of the initial dose in certain classes of wounds, from 500 units to 1,000-1,500 units. The British tetanus committee, in the same year, recommended that, additional thereto four doses, each of 500 units, should be given at intervals of seven days. This latter recommendation was responded to variously, from 40 to 90 percent,3 consequently, it is impossible to say definitely what influence multiple doses of serum had upon the lowering of the incidence of tetanus. During the fall of 1918 the strength of the primary dose to be given at the front was increased to 1,500 units, with the hope that a higher degree of immunity might be obtained. Second, third, and fourth doses were to be given at weekly intervals, the strength of each to be 500 units.3 Since the war ended soon after this last change in the administration of the serum inadequate time remained to determine whether or not any improvement resulted from it. What is of particular interest, however, is the fact that, with the increase of the number of multiple injections, the
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mortality rate progressively decreases in those contracting tetanus. There is a relationship between prophylactic injections of antitetanic serum and the prolongation of the incubation period of tetanus, which must be taken into consideration in the present connection, for it is possible the decreased mortality mentioned above might to a certain extent be attributable to cases with lengthened incubation periods; a long incubation period goes hand in hand in hand with low mortality. According to Bruce, 3 the average incubation in days in1914-15 was 13.4; 1915-16, 31.2; 1917-18, 46.19.
SURGICAL PROCEDURES
The tetanus bacillus being an anaerobe, thriving best on putrescent tissue, it follows that the early and absolute excision of such tissue, as well as foreign bodies, ranks first as a prophylactic. This was one of the great surgical lessonswhich the war taught and was not appreciated thoroughly until 1917, and after other and much less satisfactory methods had been tried out. It is true that tetanus was only one of the several kinds of wound infection for which wound excision was devised, nevertheless the agreement is general that thorough wound excision had a material influence on the incidence of tetanus following its general adoption in the spring of 1917. On the other hand, nothing occurred during the war to change the opinion obtaining prior thereto that operation should be avoided in cases of tetanus, for by the time tetanus symptoms appear there is already a general toxic condition.
Because it was recognized so frequently during the war that tetanus bacilli could lie dormant for surprisingly long periods, only to light up on surgical interference, the administration of a prophylactic dose of antitetanic serum was generally practiced prior to secondary operation on war wounds and upon manipulations incident to the reduction of compound fractures.
MODIFIED TETANUS
With the widespread use of antitetanic serum for the prophylaxis of tetanus, classical forms of the disease occurred less commonly than the modified (local tetanus). Burrows 8 states that this localized tetanus may be splanchnic, cephalic, or seated in the limbs, and explains its occurrence on the basis of laboratory experiments with animals. These experiments showed that the tetanus toxin gains access to the nervous system either by the general blood stream or by the motor nerves. The injection of antitoxin in cutting off approach by the blood stream permits the toxin to find access only along the motor nerves. Hence it can cause only local spasticity.
MEMORANDUM ON TETANUS, AMERICAN EXPEDITIONARY FORCES
Based upon the facts outlined above, the following information was promulgated to the medical officers of the American Expeditionary Forces for their guidance in the prevention and treatment of tetanus : 9
Spores of the tetanus bacillus are universally distributed in soil that has been cultivated and manured. In consequence they are virtually constant throughout the battle fieldsof France. And since the soil inevitably gets upon the clothes and bodies of soldiers, all wounds must a priori be regarded as probably contaminated with tetanus. Tetanus spores
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in such wounds may at any time develop into tetanus bacilli and produce tetanus toxin,with consequent development of symptoms of the disease.
The tetanus bacillus thrives particularly on injured tissue. Wounds with tissue destruction, especially if there are pyogenic infection and blood clots, are particularly dangerous. Wounds may appear clean and heal by primary intention and nevertheless harbor tetanus bacilli; or tetanus spores may remain latent in such wounds, and when secondary operation produces tissue death or small blood clots they may develop and cause tetanus.
Tetanus antitoxin.- Tetanus antitoxin neutralizes, multiple for multiple, the toxin of the tetanus bacillus. However, it must be remembered that the toxin produced by the bacillus becomes very rapidly attached to the nerve cells which it injures, and toxin which has become fixed in this manner is amenable to the neutralizing action of the antitoxin to a very slight extent only or not at all.
For this reason, the prophylactic value of tetanus antitoxin has been established beyond doubt, but the success of its therapeutic use depends largely upon an early diagnosis and proper administration.
Prophylactic use of tetanus antitoxin.- A prophylactic of 1,000 units of tetanus antitoxin will be given to all wounded, whatever the nature or severity of the wound. This should be done as soon as possible after infliction of the wound, preferably at the battalion aid station. Some of the antitoxin will be furnished in syringes, but it is impossible to provide all of it in this form. Care will be taken, therefore, that battalion aid stations and other advanced dressing stations be provided with a supply of sterilizable 10 c.c. syringes and suitable needles for serum provided in bottles.
Since tetanus antitoxin is eliminated by the body within 10 to 14 days and since the incubation time of the disease varies greatly, depending upon fortuitous circumstances, such as the extent of tissue death and secondary infection, at least one subsequent dose of 1,000 units will be given after an interval of 7 days. It is recommended that officers giving these repeated doses take cognizance of the memorandum on anaphylaxis and be guided in their serum administration thereby.
Tetanus antitoxin will also be administered as a routine measure in the following conditions: 1. Upon the recognition of "trench foot" with or without skin abrasion. 2. In case of frost bite. 3. During operations performed under conditions of unsatisfactory asepsis, e. g., emergency operations, operations for hemorrhoids, fistulte, or any conditions where fecal contamination is a possibility. 4. During secondary operations necessary in the course of treatment of wounds received 7 or more days previously. 5. Following the manipuations incident to the reduction of compound fractures or dislocations, after the removal of adherent drains or any other procedure resulting in disturbance of the healing process in a woundl 7 or more days old.
The antitoxin will be administered subcutaneously, preferably over the lower abdomen by or under the immediate supervision of a medical officer.
All injections, with amounts and dates, signed by the officer administering them, will be entered on patient's field medical card.
In addition to the above regulations for the routine administration of tetanus antitoxin, medical officers are advised that two injections may not be sufficient in all cases. In severe injuries where prolonged suppurative processes persist, especially when fecal contamination of the wound per rectum or through intestinal fistulae is present, and when much tissue necrosis occurs, three or even four doses may be indicated. The attending medical officer must bear this in mind and exercise judgment accordingly in the individual case.
Early diagnosis.- As stated above, the success of specific treatment in tetanus depends primarily upon early diagnosis. For this reason surgeons should be constantly on the alert for local manifestations which often precede the development of generalized tetanus. Since the toxin is conveyed to the central nervous system by way of the nerve trunks, there may be early rigidity, spasticity, or even twitching of the muscles surrounding the wound--which occasionally may be accompanied by pain and a local increase of reflexes. These symptoms,as well as "sore throat," "stiff neck," early trismus, and in head wounds, facial paralysis, should be constantly watched for and nurses should be instructed to keep this in mind whenever dressing a wound or doing other services for patient.
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By conscientious attention to early manifestations of this nature life may be saved. Immediate treatment should be instituted in all doubtful cases.
Treatment with antitoxin.- When the early symptoms of tetanus have been recognized or when the disease has distinctly manifested itself, energetic treatment with antitoxin should immediately be instituted. There are many different ways of administering the antitoxin, and it is by no means plain as yet whether the subcutaneous, intravenous, or intrathecal method will eventually prove to be the most efficacious. However, it would seem that in cases recognized early a combination of immediate intrathecal and intramuscular injections is advisable.
In every case strongly suspected of being tetanus at least 5,000 units of tetanus antitoxin should be given intrathecally as soon as possible. This is done by lumbar puncture, preferably under an anesthetic. The serum should be injected slowly and in volume should about replace the amount of spinal fluid withdrawn. When little or no spinal fluid flows, as occasionally happens, a relatively small volume of serum should be injected (about 5 c. c.), and this very slowly. In all cases intrathecal injections should be done slowly, either by gravity or directly with a syringe, and repeated within 12 hours if the first volume injected does not contain 5,000 units. After such injections it is a good plan to raise the foot of the bed and remove the pillows. At the same time 8,000 to 16,000 units of antitoxin should be administered intramuscularly, with observance of all precautions spoken of in the circular dealing with dangers of anaphylaxis. The intrathecal injection will often give rise to meningeal irritation and turbid spinal fluid, which, however, need cause no alarm.
Both the intrathecal and intramuscular injections may be repeated daily for two or three days. It is rarely necessary to inject subsequent to this, because any effect the antitoxin will produce results from the first injection, since antitoxin is not completely absorbed for several days and is not eliminated completely for 10 or 12 days.
Supplementary treatment.-Morphine and other sedatives should be given with the idea of resting the patient, and they should be administered in doses sufficient to give the most adequate physiological effect compatible with safety.
As soon as the diagnosis of tetanus is made the case will be reported by telegram to the chief surgeon, A. E. F.
REFERENCES
(1) Sick and Wounded Reports to the Surgeon General. On file, Historical Division, S. G. O.
(2) McConkey, A. T.: The Prophylaxis of Tetanus. British Medical Journal, London, December 11, 1915, ii, 849.
(3) Bruce, Major General Sir David: Tetanus. War Medicine, Paris, 1918-19, ii, No. 5, 724.
(4) Cummins, S. L., and Gibson, H. Graeme: An Analysis of Cases of Tetanus Occurring in the British Armies in France between November 1st, 1916, and December 31st, 1917. Lancet, London, March 1, 1919, i, 325.
(5) Tulloch, W. J.: Report of Bacteriological Investigation of Tetanus Carried out on Behalf of the War Office Committee for the Study of Tetanus. Journal of Hygiene, Cambridge, 1919, xviii, No. 2, 103.
(6) Bruce, Major General Sir David: Importance of Early Prophylactic Injection of Anti- tetanic Serum in Trench Foot. British Medical Journal, London, January 13, 1917, i, 48.
(7) McConkey, A. T., and Homer, Annie: On the Passive Immunity Conferred by a Prophylactic Dose of Antitetanic Serum. Lancet, London, February 17, 1917, i. 259.
(8) Burrows, H.: Modified Tetanus. Lancet, London, January 27, 1917, i, 139.
(9) Bulletins on Transmissible Diseases and the use of Therapeutic Sera, American Expeditionary Forces, May, 1918.
