Part 6

We very soon recognized in consultation with the obstetricians that the pregnant woman was in a really dangerous condition if she contracted influenza. She was likely to have a termination of her pregnancy in the height of the infection, no matter how recent or how remote pregnancy had taken place. If pregnancy did not terminate, the chances of recovery were less than those of the non-pregnant woman; if it did terminate, the chances for recovery were still less. To the pregnant woman with pneumonia very little hope of recovery could be offered. I am indebted to Dr. Paul Titus, of the Obstetrical Department of the School of Medicine, University of Pittsburgh, for a report which includes the cases seen by himself and his assistant, Dr. J. M. Jamison, during this epidemic. Dr. Titus was kind enough to include in his report certain conclusions which merit consideration. The report is as follows: “A series of 50 cases, at all stages of gestation. Interruption of pregnancy occurred in 21, or 42 per cent., of the cases; 29, or 58 per cent., in which pregnancy was uninterrupted. Mortality of pregnant women developing epidemic influenza is higher than that of ordinary individuals, even though their pregnancy is undisturbed, since 14 of the 29 in whom pregnancy was not interrupted died, an incidence of 48–2/10 per cent. If a pregnant woman miscarries or falls into labor, the mortality increases to 80–9/10 per cent. (17 of the 21 in whom pregnancy was interrupted died). The period of gestation has less influence on the outcome than the interruption itself. Of 10 at term, 3 lived and 7 died after delivery.

“Two main features of this condition as a complication of pregnancy are: First, pregnant women developing epidemic influenza are liable to an interruption of their pregnancy (42 per cent. aborted, miscarried or fell into labor); second, the prognosis, which is already grave on account of the existence of pregnancy, becomes more grave if interruption of pregnancy occurs.

“The cause of the frequency of interruption of pregnancy is probably a combination of factors: (1) The theory of Brown-Sequard that a lowering of the carbon-dioxid content of the blood causes strong uterine contractions sufficient to induce labor. (2) The toxæmia causes the death of the fœtus, particularly if not mature, when it acts as a foreign body and is extruded (10 premature fœtuses were born dead, while 1 was born alive, although 9 out of 10 at full term were born alive and survived).

“The cause of the frequency of death following interruption of pregnancy is also due in all probability to a combination of factors: (1) Shock incident to labor. (2) Increase from muscular labor of carbon-dioxid in blood already overloaded by the deficiency of the diseased respiratory organs. (3) Sudden lowering of intra-abdominal pressure by the delivery. (4) Lowering of blood pressure by the hemorrhage of the delivery. (5) Strain of labor on an already impaired myocardium.”

If one had been told a year ago that an epidemic could occur which would result in the death of 60 per cent. of all pregnant women affected, it would have been thought too unlikely to warrant any consideration. Though the effect upon pregnancy of the acute infectious diseases forms an important chapter in the pathology of pregnancy, it seems that the profession, and in this the obstetrician is no exception, has never realized how pernicious and tragic the results of an influenzal epidemic can be in a community. From the experience in previous epidemics we cannot but feel that the infection in the present epidemic was unusually fatal. Whitridge Williams (“Text-book of Obstetrics”) speaks of the interruption of pregnancy as having occurred in 6 out of 7 cases with one observer, and in 16 out of 21 in another, while a third has found it only twice in 41 cases. However, none of these writers speaks of having had a death.

_Sequelæ_

In referring to some of the associated conditions of influenza one scarcely knows whether to consider them as complications or sequelæ. The pathological process certainly had its origin from the influenzal attack, but at times apparently assumed an inactive stage. The patient is usually free from any specific influenzal symptoms, but retains for a long time other symptoms referable to various organs, or he may have been normal for a shorter or a longer period and then suddenly develop symptoms apparently independent of the previous infection. It may be well to consider all such conditions which followed the febrile attack, whether immediately or more remotely, as sequelæ, and I shall therefore speak of them as such.

The first and probably the most interesting and confusing are the conditions found in the lungs following influenza. A chronic bronchitis, an old bronchiectasis, or a previous tuberculous lesion in whatsoever stage, may present acute symptoms and signs which are difficult to interpret. The question always arises in the individual case—is this a process due to the recent influenzal attack, or was it there before the attack? Is it of streptococcic, pneumococcic, or tuberculous origin? The history of previous diseases of the lungs may help to arrive at a diagnosis. The history of the severity of the influenzal attack is of very little help, because the apparently mildest attack may be followed by the most profound changes in the lungs, and the gravest attack with a history of definite lung infection may leave the lungs without a trace of the previous pathology. The physical examination is helpful, of course, in determining whether the lesion is at the apices or at the bases, and from this a reasonably safe inference may be drawn as to whether it is from a previous tuberculous lesion or a recent influenzal infection. The Roentgenologist depends almost entirely upon this localization. If the linear striæ are only at the apex, it is probably tuberculous; but if they are only at the base, or also at the base, it is likely to be an influenzal lung. In fact, the Roentgenologist with his present information is ready to admit that it is most difficult to speak definitely of the lungs in these cases. The possibility of confusing the post-influenzal lung with a tuberculous lesion is not peculiar to this epidemic. After the epidemic of 1889 and 1890 the same condition was observed by clinicians. Dr. Roland G. Curtin, of Philadelphia, in 1892 and 1893 conducted a series of clinics at the Philadelphia Hospital, in which he spoke of the “non-bacillary form of phthisis,” and showed case after case which he said might be diagnosed as pulmonary tuberculosis, but because of the recent epidemic and the absence of the tubercle bacillus he diagnosed them as post-influenzal lung.

In the present stage of our knowledge, many of these post-influenzal lungs will not be diagnosed properly until sufficient time is given for either the lung to clear up or the tubercle bacillus to appear in the sputum. We would emphasize the importance at the present time of finding the tubercle bacillus in all suspicious lung lesions before giving a positive opinion as to the tuberculous nature, even though the physical signs are very definite.

Another group of sequelæ is that due to thyroid disturbance, or disturbance of the endocrin system in general. Since the epidemic a number of patients have been seen who noticed an enlargement of a previously normal thyroid gland or greater enlargement of a previously hypertrophied gland. In the same way the symptoms of hyperthyroidism appeared, new in some or a recrudescence in others.

In some of these there was a disturbance of carbohydrate metabolism, as shown by an occasional glycosuria and an increase in the blood sugar, or by a possible disturbance of the suprarenals, as brought out by the administration of adrenalin hypodermatically (Goetsch test). In the application of this test in post-influenzal patients it appeared that the whole endocrin system was in a state of imbalance.

It appears to us not at all improbable that the so-called psychoneuroses of which fatigue, nervousness, irritability and tachycardia play such an important part might also be explained in the same way. These constitute a group of sequelæ which were frequently recognized after previous epidemics, and which are again coming to the foreground.

We are of the opinion, on account of the apparent absence of any specific pathology of the gastro-intestinal tract and its appendages during the attack of influenza, that the sequelæ referred to the digestive system are largely due to exacerbations of previous physiological disturbances or pathological processes. The patient with a previous peptic ulcer has a recurrence of his ulcer. The patient with an infection of the biliary tract has an acute exacerbation, or may have an attack of biliary colic. In fact, there seem to have been many more cases of this kind since the epidemic than before, and most of the patients date the time of the onset from a period soon after recovering from influenza.

Very few, if any, patients in our experience have exhibited sequelæ due to disease of the cardio-vascular or genito-urinary systems. It may be that these will appear later when the more remote effects of an acute infection are recorded.

A very commonplace sequel, but of more or less interest, is the tendency to furunculosis. Our attention was particularly called to the associated hyperglycæmia. The blood sugar readings varied from 0.2 to 0.41. There was no glycosuria, acetone or diacetic acid. We have no explanation to offer for this, although one might dilate readily on many attractive theories. The hyperglycæmia, one may add, was readily reduced by a lowered carbohydrate intake, which also had a curative action on the furunculosis.

Finally we would mention the peculiar epidemic which has been observed apparently over the world, encephalitis lethargica. We do not for a moment put ourselves on record as regarding this disease as a post-influenzal affair, but no one will deny that it has a peculiar time relation to the epidemic; and further, that its distribution is apparently identical. Its bacteriology seems to be unknown. Its local pathology in the mid-brain is not peculiar or at variance with encephalitis produced by known organisms. We have seen five cases; three of whom had had undoubted influenza, while the other two were entirely free from even the slightest suggestion of any type of illness previous to the attack. All of these cases recovered. It has been stated that following the 1890 epidemic a clinical condition was observed in Europe which bears a close resemblance to what has been termed at the present time encephalitis lethargica.

_Prognosis and Mortality of Influenza_

In giving a prognosis of influenza one has to take into consideration the peculiar manifestations of the disease, especially the possible and sudden changes which are liable to take place in the lungs. The points which lead one to feel that the outlook is grave occur in about the following order, which is also about the order of the severity of the symptoms. First, _cyanosis_. This usually appeared quite early and was considered a forerunner of definite lung infection. It may have been a symptom only of the “wet lung,” to which reference has been made, but it was usually followed with definitely recognized pathology in the chest, and it immediately made the outlook unfavorable. Second, _continuation of elevated temperature_. If the temperature fell to normal in three or four days, the outlook was, of course, good; but if it went up again, or if the temperature did not fall in that time, the chances were that there was a lung involvement, even though the chest signs were negative or only those of an acute bronchitis. Strange to say, however, when definite chest signs were once recognized, the height of the temperature or the continuation of fever was not so important a prognostic factor. Third, _increase in pulse rate_. The pulse, as was noted before, was unusually slow, even though the patient seemed desperately ill; when, however, it began to increase in rate the condition was usually very grave. Fourth, _the extent of lung involvement_. This was of very little prognostic value. Both lower lobes might be solid, and yet if there was no cyanosis and the pulse and respirations were satisfactory, the outlook was rather good. On the other hand, there might be the slightest involvement of the lung, and if the pulse were rapid and cyanosis present the outlook was grave. Fifth, _depression and stupor_, or loss of so-called “morale.” If the patient remained clear in his mind, bright and hopeful, no difference how extensive the involvement or how grave the symptoms, the prospect of recovery was better. This is, of course, not peculiar to influenza, but it seemed particularly striking during the epidemic. Sixth, _a gradually rising rate in respiration_, which often was not more than two per minute per day, if progressive, even in the absence of other untoward signs, conveyed a serious prognosis.

Our mortality among the civilians in comparison with the soldiers was exceedingly high. The first cases seen by us were among the soldier patients sent to the hospital. These were as fine a lot of healthy young men as one can well imagine. They came to the hospital comparatively early in the infection. After the first week it appeared as though our experience would be entirely different from those in other localities, for we had very few deaths. In another week our mortality began to rise, but never as high as among the civilians, as will be seen by the following figures.

Of the 153 soldiers 87 were without lung involvement, and of these none died; 66 had lung involvement, and of these 16 died. Mortality among the 153 was 10 per cent. Of the 394 civilians 157 were without lung involvement, and of these 1 died; 237 had lung involvement, or some other complication, and of these 93 died. Mortality among the 394 was 23.6 per cent.

It will be seen that the mortality in the civilians was more than twice as high as in the soldiers. It has already been mentioned that the soldiers were ordered to the hospital promptly. The civilian patients, on the other hand, were later in coming to the hospital, some of them appearing when they had already developed serious complications. Another factor in determining the mortality were the ages of the patients. The soldiers ranged from 18 to 34 years, with an average of 20 years. The civilians ranged from 6 months to 73 years, with an average of 30 years. Generally speaking, the greater the age the higher was the mortality.

A third factor which should be considered in determining the actual mortality is the result of later complications and sequelæ. The figures as given are those of 547 patients, 110 of whom had died in the Mercy Hospital and 437 of whom had been discharged therefrom between September 22 and November 30, 1918, the length of the quarantine. Those who were discharged had been up and about for a week or 10 days before leaving the hospital. From our experience with post-influenzal patients admitted to the Mercy Hospital since November 30, we are of the opinion that some of the patients discharged before November 30 as recovered may have later developed sequelæ which might have proved fatal. No follow-up system has been pursued as yet which enables us to speak definitely and statistically of the present condition of those discharged.

This compilation does not readily lend itself to drawing any more specific conclusions, but we cannot desist from expressing our opinion that in the clinical study of this recent epidemic we find very little that may not have been observed by clinicians in previous epidemics.

THE URINE AND BLOOD IN EPIDEMIC INFLUENZA

By PETER I. ZEEDICK, M. D.

Epidemic influenza, unlike other acute infectious processes as diphtheria and scarlet fever, seemingly attacks the kidney in a rather mild manner. This statement refers only to the uncomplicated cases, as other bacterial or toxic agents do play a part in the nephritides occurring so often with the pneumonias or other complications following influenza. It is, however, true that in many simple epidemic cases there is evidence of a transient mild nephritis, or possibly, more correctly stated, a nephrosis. Some writers observed albuminuria in 80 per cent. of the cases, while the incidence in other reports varies from 4 to 66 per cent. It is not always stated with reference to these figures that the patients clinically were free from the common complication—pneumonia. The findings of various observers differ greatly, but they all agree that acute nephritis as a serious sequel is somewhat rare.

In the literature of the past epidemics general acknowledgment has been accorded to the presence of albumin in the urine during the acute stage of the disease. Many times this has received no further notice or comment than “febrile albuminuria.” The association of occasional hyaline and granular casts has also been mentioned. One is impressed with the fact that the older observers laid but little emphasis on the urinary findings. It also seems to be true that nephritis as a clinical entity is not prone to follow the epidemics. In general, our conclusions from the last epidemic are about the same.

The data for this paper was obtained from examination of 994 specimens of urine from 750 patients; of this number 517 specimens were examined at the Magee Hospital, where members of the S. A. T. C., all young men, were treated, and 447 specimens from the Mercy Hospital, where, in addition to the S. A. T. C., we had men, women and children. On account of the large amount of material and work on hand, as a rule only one specimen of urine was examined from each patient, but where complications were suspected repeated daily examinations were made. We have grouped our results in tables, so that the various points may be more readily followed.

Table I shows the urinary findings of uncomplicated influenza cases admitted to the wards of the Mercy Hospital. None of these cases developed pneumonia and, after running the usual course, recovered. We would call attention to the fact that 25 per cent. showed albuminuria. The amount of albumin was never excessive, and very often was little more than a faint trace. On the other hand, we have had a few patients where a previous kidney lesion was known to be present, and naturally in these cases a heavy cloud of albumin was met with. The albuminuria was almost always a transient affair, lasting only during the acute part of the illness, and would rightly come under the class of febrile albuminuria. We regard it as being more the evidence of nephrosis than a nephritis. As a rule, the time for the appearance of albumin was after the fever had been present for at least two or three days. One rarely met with it in the short attacks of influenza where the temperature came to normal in less than 72 hours. A certain time factor appeared to be necessary in order for the nephrosis to develop. Another point of interest is the presence of red and white blood cells seen relatively frequently during the early days of the illness. One wonders if this finding is analogous to the bleeding from the nose and lung so often met with at the onset of the disease. The red blood cells were seen microscopically, and only very rarely did we encounter a smoky urine.

TABLE I

URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MERCY HOSPITAL

───────┬─────────┬───────────────────────────────┬──────┬──────┬────── Day of │Total No.│ │ │ │ Disease│ of │ SPECIFIC GRAVITY │ Alb. │R.B.C.│Casts │Specimens│ │ │ │ ───────┼─────────┼───────┬───────┬───────┬───────┼──────┼──────┼────── │ │1001–10│1011–20│1021–30│1031–40│ │ │ ───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼────── 2│ 118│ 8│ 31│ 61│ 18│ 29│ 17│ 8 3│ 97│ 8│ 15│ 62│ 12│ 23│ 10│ 11 4│ 51│ 9│ 22│ 17│ 3│ 11│ 7│ 5│ 24│ 4│ 2│ 14│ 4│ 5│ 3│ 4 6│ 11│ │ │ 8│ 3│ 4│ │ 7│ 25│ │ 10│ 14│ 1│ 8│ │ 8│ 12│ │ 2│ 8│ 2│ 6│ │ 3 9│ 4│ │ 2│ 1│ 1│ 2│ │ 18│ 2│ │ 1│ 1│ │ │ │ ───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼────── Totals │ 344│ 29│ 95│ 186│ 44│ 88│ 37│ 26 ───────┴─────────┴───────┴───────┴───────┴───────┴──────┴──────┴──────

TABLE II

URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MAGEE HOSPITAL

───────┬─────────┬───────────────────────────────┬──────┬──────┬────── Day of │Total No.│ │ │ │ Disease│ of │ SPECIFIC GRAVITY │ Alb. │R.B.C.│Casts │Specimens│ │ │ │ ───────┼─────────┼───────┬───────┬───────┬───────┼──────┼──────┼────── │ │1001–10│1011–20│1021–30│1031–40│ │ │ ───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼────── 1│ 101│ 6│ 22│ 49│ 24│ 5│ │ 3 2│ 127│ 1│ 17│ 75│ 34│ 13│ │ 3 3│ 82│ 3│ 13│ 55│ 11│ 13│ 1│ 4 4│ 36│ 1│ 14│ 18│ 3│ 4│ │ 2 5│ 40│ 2│ 9│ 24│ 5│ 6│ 1│ 2 6│ 23│ 1│ 5│ 15│ 2│ 7│ 1│ 3 7│ 5│ │ 1│ 4│ │ 3│ │ 2 8│ 5│ 1│ │ 4│ │ │ │ 9│ 2│ 1│ │ 1│ │ │ │ 10│ 10│ 1│ 3│ 5│ 1│ 2│ │ 1 11│ 3│ │ │ 3│ │ 2│ │ 1 12│ 3│ │ 1│ 2│ │ 2│ 1│ 13│ 1│ │ 1│ 3│ │ │ │ 14│ 1│ │ │ 1│ │ │ │ 15│ 5│ │ 1│ 4│ │ │ │ ───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼────── Totals │ 447│ 17│ 87│ 263│ 80│ 57│ 4│ 21 ───────┴─────────┴───────┴───────┴───────┴───────┴──────┴──────┴──────

The results shown in Table II illustrate the urinary findings at the Magee Hospital, and, as in the previous table, include cases of influenza which did not develop pneumonia. The specimens examined were obtained from young, healthy men, between the ages of 20 and 32, and showed albumin in 13 per cent. of the cases. This age factor probably accounts for the lower incidence of albuminuria for this group.

TABLE III

URINE ANALYSIS IN CASES OF PNEUMONIA (INFLUENZAL) AT THE MERCY HOSPITAL