Page 432 LANCET,] DRS. T.H. OLIVER & D. V. MURPHY :INFLUENZAL PNEUM0NI;\. [FEB. 21, 1920

By Dr T.H. OLIVER, M.A., B.Ch. Cantab., M.D., Vict.,
Resident Medical Officer, The Royal Infirmary,
Manchester;
and
D.V. MURPHY, M.B., Ch.B.N.U.I.
Captain, R.A.M.C.
————
IN view of the possibility of a further outbreak of influenza accompanied by broncho-pneumonia, another method of combating the extreme toxaemia and anorexia appears to be worthy of record, more particularly so as the clinical importance of the latter has recently been discussed by Professor J.S. Haldane1. It is noteworthy that in his paper he lays especial emphasis on the primary need of oxygen in solution in the blood.
Theory Underlying the Treatment
There occurred in Busrah in June and July, 1919, a severe epidemic of influenza, most marked among Indian troops, and accompanied in many cases by an exceedingly toxaemic and fatal broncho-pneumonia. It is unfortunately impossible to give statistics of the mortality of the epidemic, but its extent may be gauged from the fact that in one large Indian hospital in which the influenza cases were segregated in special huts the death rate was over 80 percent in the pneumonia cases with toxic symptoms.
So useless were the usual remedies tried in this latter class of case that we felt justified in giving a trial to any method which held out a prospect of success. It had been observed by one of us (T.H.O.) some years previously that an ammoniacal solution of hydrogen peroxide had, in the presence of a catalyst (copper), a remarkable oxidising power on morphin2. Further investigation, as yet unpublished, showed that many other substances were similarly oxidised by this solution, the power of which appeared to depend primarily on the formation of nascent oxygen.
We thought that use might be made of this reaction if the H2O2 were given intravenously, in this instance employing the well-known catalytic powes of haemoglobin as a substitute for the copper, and we hoped thereby, not only to supply oxygen to the tissues with greater rapidity than by the ordinary methods, but also to render the circulating toxins inert by oxidation. The obvious danger was gas-embolism, against which most text-books warn those using H2O2 even to wash out serus cavities. We believed, however, in the first place, that pure oxygen if given suficiently slowly, would be absorbed before any embolic symptoms developed, and secondly, that the air-embolism known to surgery is really a misnomer for nitrogen embolism.
Effect on Patients
The first case was an Indian with broncho-pneumonia of influenzal origin and intensely toxaemic. He had been delirious for two days previously, and was selected as being the worst case in the ward and to all appearances moribund. Two ounces of H2O2were diluted with 8 ounces of normal saline, and the solution made slightly alkaline with 5 minims of liquor ammonia. This produced a faintly effervesceing solution. The median cephalic vein was exposed by open dissection, and the solution infused through a glass cannula attached to a Rogers cholera apparatus.
The solution was infused slowly, a complete stop being made for half a minute in every four. Small bubbles were allowed to enter the vein unchecked, but if a large accumulation of oxygen appeared in the cannula, the transfusion was checked for about a minute until it had gradually entered the vein. The whole transfusion lasted for 15 minutes. The patient showed no signs of discomfort until towards the end of the operation, when he became slightly restless. This, however, passed off in a few minutes, and there was no other untoward symptoms except a moderate rigor which occurred two hours later. After the rigor the temperature, which had been 101.8o, fell to normal and remained so for 36 hours, when it again rose to 101o. The latter rise was not accompanied by toxic symptoms and the temperature gradually fell to normal in the course of the next ten days. The change in the mental condition was remarkable, the patient, who previously had had to be tied in bed owing to delirium, was within six hours of the injection sitting up and asking for food; he slept well the next night and from that time improved in every way, eventually being invalided to India as a walking case three weeks later.
Encouraged by the apparent success in this case, we tried the method on 24 others — cases of influenzal pneumonia — selecting always those whose condition was apparently hopeless. Of the total of 25 cases, 13 recovered and 12 died, a mortality of 48 percent. Of the 12 who died, 9 showed no visible effect for either good or ill. In 3 there was a temporary improvement. One case only died within five hours of the infusion, during a rigor. One of the cases had four injections at intervals of three to five days without any signs of gas embolism, nor did we find any signs of such embolism post mortem. Of the 13 who recovered, 10 were delirious at the time of infusion and had to be held down in bed. Three were comatose from toxaemia.
The average respiration rate before the operation was 46 per minute, the greatest being 60 and the least 28. Within 24 hours of the infusion the average rate was 31.5, the greatest fall being from 60 to 24. The noticeable feature, however, was a steadying and deepening of the respiration and a great lessening of the discomfort. The average pulse-rate before infusion was 118. 24 hours later, the average was 98.
The temperature in this epidemic was, apart from complications such as malaria or effect of heat, rarely high and usually 101o-103o. In all cases but one, the injection was followed by a rigor, after which (except in two of the cases) the temperature fell to normal. Of the two exceptions one remained with the same temperature as before, the other fell from 102o to 100o. The afebrile period lasted from usually for 18-36 hours, after which the temperature again rose to 99o-101o, and fell by lysis in 4-7 days.
At this juncture we would point out that the occurrence of a rigor or a fall by crisis is exceeding rare in Mesopotamia in cases of pneumonia. Neither of us remember such an occurrence in an experience of 3½ years among British and Indian troops. As regards the toxaemia, we believet hat the frequent occurrence of a rigor and a complete or partial crisis, combined with a rapid improvement in the patient’s general and mental condition indicated that this was overcome in many instances. Whether this was by merely supplying oxygen to devitalised tissues, or whether direct oxidation of the circulating toxins took place, it is not easy to say. It is difficult to believe, however, that so small a quantity of oxygen as is contained in 2 oz. of H2O2 could produce these effects other than by its nascent oxygen, and this view is supported by a trial we made in a case of toxaemia arising from suppurating inguinal glands in which there was no question of anoxremia. Here the general improvement which so rapidly took place could only be ascribed to direct oxidation.
The accompanying four charts will give some idea of the reactions obtained in one fatal and three recoveries: in the first it will be seen that four injections were given, the first two of which produced a rigor and temporary improvement. In the second two injections were given, each producing a rigor and some improvement both in pulse and respiration rate. In the third and fourth the injection was followed almost immediately by a rigor and subsequently by a crisis. In all these cases there was marked slowing of the respiration rate after the injection.
Technique
A strength of 2 oz. H2O2 in 8 oz. of normal saline was usually used. In one case 3 oz. of H2O2 was used without any ill effect. Fifteen minutes was allowed for transfusion aand this was checked temporarily every four minutes, or whenever large bubbles of oxygen appeared in the cannula, or if the patient became at all restless. Small bubbles entering the vein did not appear to do any harm. In one case the patient struggled so violently in his delirium that the cannula slipped out and the distal ligature came off. On pressing the vein above two distinct streams could be seen to issue from the wound, the one above bright red and frothing, the other deep blue.
The epidemic ceased almost as suddenly as it had begun, so we were unable to try the method on earlier cases or to give a more extensive trial to repeated injections.
Conclusions
1. H2O2 can be given intravenously without gas embolism being produced.
2. The anoxremia is often markedly benefited.
3. The toxemia appears to be overcome in many cases.
4. The mortality (48 percent) compares very favourably with the 80 percent in similar cases not so treated, and more so when it is remembered that we only treated the most severe and apparently hopeless.
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1. Brit. Med. Jour. July 19th, 1919.
2. Medical Chronicle, July 1914.