Part 8

The second group, or those showing a leucopenia throughout their course, was by no means an unusual thing. This is a cardinal point—in fact, one of the most striking clinical features of the epidemic. The leucopenia here does not have the prognostic value that it seems to have in the group just referred to previously. We have observed cases go through a pneumonia with 4,000–5,000 white cells in a relatively easy manner. When, however, the leucocytes fall to 3,000 or under, one may be reasonably sure that the outcome is doubtful, even with the general condition of the patient at the time favorable. In the pneumonias of this group which died the leucocytes have always fallen to about 2,000 cells. We have a number of observations taken from one-half to four hours before death showing counts in the immediate neighborhood of 2,000, but never below this number. Where recovery has taken place the cells go forward to the normal, more or less keeping pace with the general clinical picture.

Of group three there is not much to say, except that on one hand it tends toward a leucocytosis, and on the other to a leucopenia. This group comprises a considerable number of the pneumonias. We are not in a position to say anything regarding the relative mortality of this group. The development of a leucopenia from these cases after a period of some stability in the leucocytic curve is of bad prognostic import. Not infrequently we have noticed rather wild abrupt rises to 20,000 in the leucocytes toward the late half of the disease. This curve was nearly always sustained until the end, which, as a rule, was recovery.

We do not need to consider at any length the effect on the leucocyte count of complications not of lung origin. Acute sinuses in head, otitis media and meningitis always produced a variable moderate leucocytosis. The change was not so marked in meningitis, as our cases were all preceded by a pneumonia which had independently invoked a slight leucocytic response. As a complication of the pneumonia we have noted an abrupt rise following an acute pleuritis with effusion, and similarly after the onset of an empyema. These complications seemed to be able to induce a leucocytosis with more certainty and ease than the more serious pneumonic condition. Possibly, as they occurred toward the end of the infection, the toxic factor of the epidemic influenza was more or less spent, and the secondary invader had a freer hand to act in its normal way.

Differential counts were made in 194 cases, including influenza, influenzal pneumonia and influenzal complications. We have taken the average percentage of each type of cell for the groups, which are purely numerical divisions based on the leucocytic count. No differentiation is made for the various clinical divisions of the epidemic in the following table:

LEUCOCYTES 2,000–8,000. P. E. L.M. S.M. Trans. Total counts 86 66% 1% 13% 17% 3%

LEUCOCYTES 8,000–10,000. P. E. L.M. S.M. Trans. Total counts 33 69% 1% 11% 16% 3%

LEUCOCYTES 10,000–20,000. P. E. L.M. S.M. Trans. Total counts 45 76% 2% 10% 19% 3%

LEUCOCYTES 20,000–30,000. P. E. L.M. S.M. Trans. Total counts 17 79% 2% 8% 7% 4%

LEUCOCYTES 30,000–40,000. P. E. L.M. S.M. Trans. Total counts 13 85% 1% 5% 6% 3%

The differential count in general indicates an increase in the polymorphonuclear leucocytes as the total leucocytic number increases. This is really what one would expect. There also seems to be an increase of the large mononuclear cells, with a slight diminution in the small mononuclear elements, particularly in the count below 10,000. Abnormal cells were encountered very seldom. One can hardly say that the epidemic has a characteristic differential blood picture, except, perhaps, that an increase of the large mononuclears is present in the low counts. This, however, may hold true for any leucopenia.

_Conclusions_

1. Epidemic influenza is often accompanied by a transient slight albuminuria with a few red blood cells and casts. Acute nephritis as a clinical entity does not appear to be other than a rare sequel.

2. Epidemic influenza tends to produce a leucopenia.

3. A leucocytosis in influenza, as a rule, indicates a secondary infection.

4. The pneumonia following influenza shows, as a rule, but a very moderate leucocytosis, while, on the other hand, the presence of a leucopenia is by no means infrequent.

We are greatly indebted to Miss R. Thompson, Messrs. Mock, Frost, Marshall and Scott for their assistance in this work at the Magee Hospital.

THE TREATMENT OF INFLUENZA

By W. W. G. MACLACHLAN, M. D.

One may frankly say there is no specific treatment for influenza. Possibly we are in error in introducing the discussion, particularly on treatment with such a definite and unsatisfactory conclusion. The same statement has been made after all the previous pandemics, and one wonders whether a like remark is going to apply to the next similar scourge. The past two or three months should bring to the medical profession a certain humility which should stimulate a keener sense of research, especially as we now have at our disposal highly organized laboratories where unsolved problems can be viewed from almost any angle. Yet we are really, save here and there, putting our forces together in the study of the disease. It is obvious that a fleeting epidemic makes a most difficult subject for study, especially during a time when there is a paucity of physicians. May we not hope, however, that some researches on the disease may be forthcoming, so that we may safely feel that at least preventive or protective measures will be possible?

There is no one who is able to say that this or that drug has not been thoroughly tried. The alkalies, salicylates, antipyretics, quinine and the sedatives have all been freely used in the last as well as the present epidemic. Each group of drugs has its following, although it appears to be a general rule in this epidemic to use the antipyretics (coal tar products) as little as possible. From the distant past we have numerous records of treatment. Willis (1658) emphasized the value of sweating and the use of diaphoretics, but at the same time he states that in mild cases the cure is left to nature; Sydenham (1675) claimed considerable value in fresh air. He also paid more attention to restricting the diet, and was not favorable to the use of anodynes. One certainly obtains the impression from the records of past epidemics that many of the general principles in treatment were similar to what are now in vogue. Medicinal remedies, of course, varied greatly, but to enumerate them would be merely giving a résumé of the progress of therapeutics. Sufficient is it to say that influenza has certainly, since the earliest days, given therapeutists an ample opportunity to test their wares.

The outstanding respiratory complication, pneumonia, has added a very undesirable phase to the disease. In fact, the greater part of the mortality was due to this serious sequela. Some interesting points have been brought out in serum and blood therapy for this type of pneumonia. The use of whole blood or serum from convalescent patients in cases of pneumonia opens up a new and not unlikely fruitful means of treatment. The method of treatment possibly may be applicable as an emergency measure in other diseases, as has been shown in the case of scarlet fever and poliomyelitis. We also have the anti-pneumococcic sera available for therapeutic use. The drugs and the general treatment of the pneumonia are virtually the same for the last two epidemics.

The protean manifestations of the 1890 epidemic, with its unusual nervous sequelæ, have not been seen to any extent, as far as we yet know. In fact, the present epidemic appears to be relatively free from complications other than those occurring in the lung during the acute course of the disease. Hence, in all likelihood, there will be less of the nervous after effects to be treated. It is, however, too early to hope that the nervous system is going to escape.

In another part of this volume the vaccine therapy is discussed in detail, so that we shall not repeat what has been brought out in that article. We would, however, emphasize the value of honest and accurate clinical reports of the use of vaccines, in order to establish their present status in epidemic influenza. Overestimation and commercialism are very likely to ruin a method of treatment, even when it may be of value in a certain phase of the disease. If we do not carefully weigh the pros and cons of the vaccine treatment in this epidemic from a purely scientific and coldly neutral attitude, we are simply doing the public and ourselves an injustice.

The treatment of influenza as the disease presented itself to us in this community will be considered under three divisions—acute influenza, pneumonia, and other complications.

_Acute Influenza_

There is one important thing to be done in the treatment of influenza, whether the infection be mild or severe. Have the patient go to bed as soon as possible. In most of the acute attacks the individual went to bed of his own accord; but there were, unfortunately, too many instances where the patient refused to surrender, trying, as we say, to fight the attack. Some appeared to be able to accomplish this feat. But how many of our cases of fatal pneumonia can be clearly linked up with this group of the mild or subacute preliminary course? No matter how light the attack may appear to be, the patient should be told of the necessity of remaining in bed until the pulse, respiration and temperature have returned to the normal and remained normal for at least five days. At the onset a hot bath, with care to avoid chilling, followed by a drink of hot lemonade and a Dover’s powder, gave considerable relief to the patient.

The value of good nursing cannot be overestimated. The nurse must see that the patient is always well covered and kept warm, not even permitting him to rise in bed to reach for a drink; also the regulation of the temperature of the room should be carefully watched. The main point is to have plenty of fresh air. We have noticed that the patient appeared more comfortable if the air was slightly warmed. Water should be given at regular intervals. Under no consideration should an acute influenza case be allowed to get up to go to the toilet.

At the onset, and while the febrile attack is still present, there is little desire for food—but one does not need to worry about the question of nourishment in such an acute illness. Milk, cream, cocoa, gruels and fruit juices may be given at first, and as the fever subsides the diet increased. We have found that the appetite returned to normal very readily. In view of the urinary findings indicating a slight transient nephritis, meat broths are to be avoided until the convalescent stage is reached. We have been very guarded in recommending cold sponging in acute influenza. As a rule, it was not necessary. The icebag to the head is often of great value in the intense headache, which is so frequent. It is our opinion that in the treatment of uncomplicated influenza what has just been mentioned constitutes the important part. Most physicians would agree with this. However, when we advance to drug therapy, we come into the personal realm of likes and dislikes of drugs and methods of usage.

We do not intend in any way to give our views in a dogmatic manner, nor to touch upon all of the remedies that have been advanced. At the onset of the disease a moderate calomel purge, followed by a saline, was given in all cases. We were practically free from the so-called intestinal type of influenza which was seen in some other communities, consequently we did not hesitate to use calomel. Castor oil or magnesium sulphate was given afterward, as was found necessary. Abdominal distention was rarely seen, and when it occurred a plain soapsuds enema with turpentine was administered.

Quinine sulphate (gr. iii-v, three times a day) combined with phenyl-salicylate (gr. v) was a routine measure. We often noticed deafness after a very few doses of quinine. It was then discontinued. Acetyl-salicylic acid (gr. v, three to six times a day) seemed to have a palliative effect on the severe headaches, although during the height of the disease the general muscular aching did not appear to be relieved by its use. It was not used routinely. These drugs possibly made the patients more comfortable, but we were very skeptical as to their influence on the general infection. The raising of the leucocyte count by quinine in influenza appears very unlikely. The use of alkaline salts has been a general procedure, particularly as we are now on the alkaline wave of therapeutics. Sodium bicarbonate was added to the drinking water of all patients (two drams to the quart). We gave this salt for its diuretic effect. In a few cases more active diuresis by the alkalines was readily and easily produced by the use of “imperial drink” three or four times a day. We felt that good kidney elimination was of considerable importance.

The use of tartrates and citrates, as in “imperial drink” in a condition where we know some kidney impairment is present, is possibly flying in the face of danger—especially in view of the fact that these salts are so available in the production of experimental nephritis. But we have only to see their application in the human in mercury bichloride poisoning, where an intense nephrosis usually develops, to fully realize that these salts may be given without danger to the kidney. We do not suggest that the kidney lesions of influenza and mercury bichloride poisoning are the same. We are merely bringing out this point of analogy in support of their use in certain desirable cases.

The respiratory symptoms gave us more concern than any other phase of the uncomplicated case. The irritating, distressing, non-productive cough suggested both a sedative and expectorant. Ammonium chloride (gr. iii-v, t. i. d.) was the usual expectorant. It seemed to increase in value with the more chronic type of case. It is our impression with those acute hacking coughs that the sedatives produced more gratifying results. Elixir terpin hydrate with heroin, codeine and occasionally morphine were preferred. When good results were noted sedatives were given liberally. Steam inhalations combined with tr. benzoin co., followed by spraying the throat with medicated liquid petroleum, gave some relief. The tendency to œdema, however, as we saw it in the cases complicated by pneumonia made us hesitate to use inhalations. Possibly the fear was groundless. Morphine (grs. ⅙) was given for sleeplessness, and it was repeated if necessary.

Cardiac stimulants were rarely needed. The tincture of digitalis was the choice, but in the uncomplicated cases was very seldom used.

At the beginning of the epidemic we prescribed whisky in almost every case. Our idea was that it would have a sedative action. At the present time we are very doubtful of its value. Toward the end of the epidemic we used it very moderately. The results obtained possibly depended for the most part upon the type of patient. Some of the soldiers asked to have it discontinued, not from any moral point of view, while others wished more frequent doses. The elderly patients seemed to appreciate this remedial agent to a fuller extent.

_Pneumonia_

The pneumonia following the original infection was, from the standpoint of physical diagnosis, often difficult of diagnosis in its early stages. The infection commencing as an influenza would at times pass imperceptibly into pneumonia, and obviously the points brought out in the previous paragraphs on treatment were applied until the diagnosis of pneumonia had been established. Some new factors were peculiar to the pneumonia and demanded further changes in the handling of the cases.

We would again emphasize the value of careful nursing to conserve the patients’ strength. They should be kept warm, well covered, with plenty of fresh air. Water should be given regularly and abundantly. The diet should be light, one depending a good deal upon the severity of the case. We believe it is safer to limit the diet to fluids while the infection is still pronounced, but as soon as the crisis has passed one may increase the diet freely and fairly rapidly.

Regular elimination from the bowel should be helped by the use of castor oil every other day, the dosage made to comply with the patient. We noticed much less abdominal distention in this form of pneumonia than one is accustomed to see in the ordinary lobar pneumonia. If distention were present, plain soap enemas with turpentine gave very satisfactory results. Turpentine stupes also are of considerable value. Rest at night is needed. When a hypnotic was necessary we gave morphine (gr. ⅙), and repeated if the desired results were not obtained.

The day is coming when we are going to isolate our pneumonia cases. This was almost an impossibility during the stress of the past epidemic, but we know that temporary and fairly satisfactory methods can be applied. Many hospitals provided for a type of isolation. In a pneumonia ward sheets stretched between the beds keep the fine spray which a heavy cough always produces from spreading over the next two or three beds. This method is simple and can be easily carried out. We feel almost certain of having seen convalescent influenza cases develop pneumonia from the adjacent pneumonia patients. As much as is physically possible, the uncomplicated influenza and the pneumonia cases should be separated. Further, it is to be kept in mind that reinfection by another group of pneumococcus is quite possible, even in a ward containing only pneumonia patients.

We did not observe any special effect of quinine, salol, salicylates after the pneumonia had developed and, therefore, these drugs were discontinued. Digitalis in the form of the tincture was at first made a routine measure, but toward the middle of the epidemic we stopped this routine usage and gave it only as it appeared to be indicated. Our impression was that the heart was not involved as it is in ordinary pneumonia. A slow, full pulse, as was so often the rule, did not seem to require digitalis. For more rapid action of the drug one of the hypodermic digitalis preparations or strophanthin was given.

Caffein sodium benzoate or salicylate seemed to be of considerable value given hypodermically every two or three hours, the last dose at 4 P. M. Its action as a respiratory stimulant and also as a diuretic was what we desired to obtain. The drug was used fairly early in the pneumonia, and although it was never prescribed routinely we gave it frequently.

Atropine was indicated whenever signs of œdema were evident. Its action was not always successful, but in certain severe cases we believe that large repeated doses of atropine saved a few lives. One-fiftieth (1/50 gr.) grain hypodermically, repeated every hour for several doses, was usually well borne. We noticed twice in each of two cases after using small doses (1/100 every four hours) a peculiar rapid cyanosis not associated with dyspnœa develop. This reaction remained, however, for only a short time, about 15 to 20 minutes, but it was rather alarming while it lasted.

The drug therapy is not very satisfactory in lobar pneumonia, and it is less so in the form of pneumonia which follows influenza. There is practically nothing essentially new in the drug and general treatment of this serious complication over what was shown in 1890, or even in the earlier epidemics, save that our nursing and hygienic measures are undoubtedly better.

The addition of an immune serum (anti-pneumococcus serum No. 1) to the treatment of pneumonia is a milestone in the history of the handling of this disease, but we must keep in mind that the pneumonia of the past epidemic was not the usual pneumococcic lobar pneumonia. That the pneumococcus was present in a great many cases is shown in another article of this series, but we also know that the B. influenzæ was present in many, and that it played an active part in the disease is evidenced by the constant low blood count or actual leucopenia. A leucopenia in true lobar pneumonia is most unusual in the United States. The rarity of Type I pneumococcus was noteworthy. We were practically unable to get any anti-pneumococcic serum which was known to be of value at the time of the epidemic, so naturally could not apply this method of treatment as was desired. About half a dozen 50 cc. bottles were in possession of the army medical officers here, but they unfortunately could get no further supply after this was used. We would have liked very much to have combined the anti-pneumococcic serum in Type I cases with the citrated convalescent blood, as was used by us during the epidemic. The anti-pneumococcic chicken serum of Kyes should also be considered. This serum has had but a very localized trial, but from competent observers who have given it to a considerable extent in some of the army camps we are led to believe that it has a very definite value. Major Lawrence Litchfield informed the writer that he had observed excellent results with Kyes chicken serum during the past epidemic in the treatment of pneumonia. This serum was not available for our use. It is to be hoped that further experience with Kyes serum will be favorable, because from the practical standpoint in the treatment of pneumonia it has many commendable features. Again, we desire to point out that the use of anti-pneumococcus sera in influenzal pneumonia may not be a fair test of their true value.

Very early in the epidemic we realized that the pneumonia was of unusual severity and most difficult to treat satisfactorily. We were at once impressed by our helplessness, particularly in those patients showing cyanosis. Nothing we did seemed to vary the course of the pneumonia after this sign was evident.

Our work in the epidemic began about October 10 on receiving a large batch of soldiers, about 100, from the Student Army Training Corps of the University of Pittsburgh. At the end of the first week several points were impressed on our mind. Firstly, in the severe cases of pneumonia; and in the early part of the epidemic most of the pneumonia was severe, the mortality was excessive, much higher than we have been accustomed to experience in Pittsburgh, where, as a rule, our hospital ward pneumonia is a very severe infection. Secondly, the wide variation in the severity of the epidemic as presented in the student soldiers coming from identical surroundings and conditions, the mildness on the one hand and the malignant character of the influenza on the other, was a very striking feature. This led to our adopting a form of treatment which was quite successful.