CHAPTER 11.

The Object and the Methods of the Investigation and the Material.

Whilst methanol poisoning has been the subject of numerous experimental investigations, clinical investigations have been scarce and to some extent very incomplete. We therefore lack an approximately complete account of the clinical features of this poisoning.

There is probably a fundamental difference between the action of methanol on man and beast. As a rule, acidosis has not been demon- strated in animal experiments, though i t has been found in certain cases (dogs) in a moderate degree. On the other hand, human beings often present severe acidosis. There have not, however, been any analytical comparisons between the acidosis and the other mani- festations. I have therefore attached great importance to the in- vestigation of this matter in the present study.

Does blindness or death occur when acidosis is severe? Or may blindness and death in certain cases be associated with a normal or slightly reduced alkali reserve? In the first case, the timely admini- stration of sodium bicarbonate should preserve the patient's eye- sight and life as it will always be possible to prevent the onset of severe acidosis. If, on the other hand, there is no such interdepen- dence betweeh acidosis and the manifestations of methanol poi- soning, no decisive effect can be expected of bicarbonate treatment.

As already pointed out, there has been no investigation of the possible reasons for the very varying tolerance of methanol shown by different persons. The opinion tha t these variations in tolerance exclusively reflect peculiarities in the individual seems unreasonable.

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This is so in the first place because the course of certain cases on record (STADELMANN and LEVY) cannot be explained by the aid of this hypothesis. I refer here to the cases in which certain persons presented a much longer latent period than their fellow-topers, and yet suffered most severely. It seems obvious that we cannot ex- plain this by assuming that some were more predisposed lhan others or that they had drunk inore methanol than others. In either case one would expect the latent period to be shortest for the patients wliose poisoning was most severe. As we shall see later, there were several patients in the present study in whom i t was possible 10 observe the same curious phenomenon just referred to. This fact, in conjunction with the observalion that several persons who had drunk much methanol did not fall ill, led me to seek other explanations for the varying course of the poisoning.

It seemed natural to ask if efhyl alcohol can influence the course of the poisoning. Seeing that most of the persons drinking methanol are topers, it is remarkable that the influence of ethyl alcohol has not been investigated. The statements made by certain authors with regard to such an influence seem to be of a speculative character.

Whilst WOOD and BULLER considered ethyl alcohol as a valu- able stimulant, others have feared it inight be harmful. Indeed, i t has been believed in some quarters that methanol was not poison- ous until it had been consumed together with ethyl alcohol (FOERSTER, 1912 p. 250).

BURGER (1912 p. 1706) had his doubts as to the wisdom of recoimnending ethyl alcohol as a stimulant:

Eknierken iniichte ich noch dass es wegen der ganz aehnlichen Wirkung des Methyl- und Aethylalkohols nicht ratsain ist, bei Vergiftungen durch Methylalkohol den Aethylalkohol als Excitans zu verwenden.

This author, as well as GETTLER and GEORGE, probably refers to the already mentioned assumption by WOOD and BULLER that ethyl alcohol may have a stimulating action. GEITLER and GEORGE write:

It is said that ethyl alcohol is indicated to replace the methyl, and that it acts as a powerful stimulant, but we doubt this.

This is all the mention I have been able to find of the effect of ethyl alcohol on methanol poisoning. There seems to be little founda-

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tion for the last opinions quoted. When WOOD and BULLER recom- mended ethyl alcohol as a stimulant, they depended on a statement by a colleague about the favourable course run by a case of poisoning treated with ethyl alcohol. As some cases of poisoning do well even without treatment, this isolated observation cannot of course serve as a proof that ethyl alcohol has a beneficial effect. But this possibility cannot, however, be dismissed forthwith.

Investigating matters niorc closely, we have found in the study by WOOD and BULLER another statement which may be of interest in this connection. They say (p. 1219) that in Great Britain dena- turated spirits containing 10 per cent. of methanol, 64 per cent. of absolute alcohol, and 2 per cent. of mineral oils were on sale. A colleague, Dr. MCWALTER, had stated that this mixture, sold with- out any restrictions, was misused as a beverage to no small extent. As far as he knew, no case of poisoning had occurred as a result of this misuse.

This statement may also indicate that ethyl alcohol is antitoxic in relation to methanol. To be sure, such a mixture must have a very intoxicating effect, and large quantities of methanol cannot be consumed for this reason. This cannot be the only explanation, for now and then amblyopia follows the consumption of very small quantities of methanol.

In an earlier study (1943) I have shown that in certain cases in which ethyl alcohol was also consunled, the poisoning was less severe than when only methanol was drutik. I have found reasons for investigating the action of ethyl alcohol on a considerable num- ber of patients, for great interest, theoretical and practical, attaches to the further elucidation of this problem.

In ordei to obtain as complete a study as possible of the clinical features of methanol poisoning I have put on record the findings of the chemical and morphological examinations of the blood as well as of the electrocardiographic investigations which have been undertaken in a certain number of cases.

Follow-up examinations of patients suffering from amblyopia have been undertaken as the information thus obtained is of crucial importance to our estimate of the prognosis. Apparently such examinations have not hitherto been carried out systematically over a long period.

It is beyond the scope of this study to give a detailed descrip- tion of the pathological-anatomical findings. I propose to deal more fully with the chemico-legal investigations as their findings are to some extent of importance to the interpretation of the interplay of the pathogenetic factors. Before an account is given of these inves- tigations in their entirety, it should be noted that volatile reduc- ing substances in the blood are always calculated as methanol.

Prominence will be given to a discussion of bicarbonate treat- ment and treatment by lumbar puncture. In my opinion, gastric lavage, which most authors recommend, and which was under- taken in most of the cases recorded here, deserves notice. As already pointed out, the value of this treatment has been questioned in certain quarters.

My material consists of 82 cases of poisoning, 75 males and seven females. Seventy-nine of the patients were admitted to hos- pital, two died in their homes, and one was treated in a German prisoners’ camp.

Most of the patients, i.e. 52, were admitted to Oslo’s City Hos- pital, UllevAl, 48 to the medical departments (Departments VII, VIII and IX), three to the eye department (Department XI), and one to a surgical department (Department 111).

Some patients were treated in the medical departments and the eye department of the Rikshospital. Lastly, some were treated in various hospitals outside Oslo.

The ages of the patients ranged from 21 to 69 years. There were 16 over the age of 50, 54 between 30 and 50, and 10 under 30. The ages of two of the patients were not stated.

Most of the patients had been healthy and strong. Three suffer- ed from open pulmonary tuberculosis, and three from pneumonia. Many were undoubtedly chronic tipplers.

Fourteen of the patients (nrs. 1, 2, 3, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21) have already been reported on by myself in a preli- minary communication on methanol poisoning (1943). As most doctors were but little familiar with the cliniLal course and treat- ment of the poisoning, I found it necessary to issue this report. For various reasons I have wished to discuss these cases in the pre- sent study also. In some of these cases the course of the amblyopia has continued to be investigated after the publication of my first

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report. These cases have therefore been investigated over a longer period than any of the others, and they are accordingly particularly well suited to illustrate the course of the amblyopia. Further, it is almost exclusively in these cases that certain biochemical investi- gations (among other things determinations of the formic acid and lactic acid in the blood) have been carried out. Owing to the shortage of assistants a t the chemical laboratories of the hospi- tals it has unfortunately not been possible a t a later date to get such examinations carried out. The results of these examinations should help us to understand the pathogenesis of methanol poisoning.

In the course of the inuestigation, every effort has been made to obtain as reliable information as possible about the circumstances associated with these cases. The hospital records of the patients' past histories were very incomplete, partly because the patients were dazed or had lost their memories, partly because circumstan- ces required prompt treatment of the patient. I t has therefore been necessary to a great extent to obtain information from others than the patient, in the first place from persons who had drunk metha- nol with him, but had not themselves fallen ill.

When the first cases of poisoning occurred in the summer of 1941, i t was not usual to admit to hospital the persons who had not fallen ill; and in many cases it was difficult to trace them. Later, however, almost all persons having consumed methanol were admitted to hospital under compulsion by the criminal police, and thus the work of obtaining information from all the participants in various carousels was facilitated.

In many cases I have obtained from the patient's relations in- formation about the manifestations of the poisoning before admis- sion to hospital. Such information was of special value in the cases in which symptoms had wholly or partially disappeared a t the time of admission. When the patient was amnesic, it would have been impossible without such information to decide whether or not he had suffered earlier from severe acidosis.

It has been necessary to a considerable extent to study the re- ports of the criminal police in connection with the cases of poisoning. These reports contained statements from several persons who in many ca6es knew the circumstances under which the poisoning had

occurred; without such police aid i t would hardly have been pos- sible to get into contact With these people.

In spite of every effort to obtain reliable information, the data collected in certain cases could not but be faulty. This was parti- cularly the case with the patients who had been drinking with persons they did not know and who lived alone.

The clinical manifestations and findings were in the main ob- tained from the hospital case records. But in some of the cases in which I had occasion to be present when the patient was admitted to hospital, I was able to make notes on manifestations which had not been recorded by the doctor on duty.

In the description of each case, I have always recorded the general condition on admisson (pulse, blood pressure, temperature and respiration) when these have been measured.

In most cases t he usual physical examination, including the investigation of the patellar, Achilles and plantar reflexes, was car- ried out. This was also the case with the examhation of the urine for albumin, sugar and blood. Wheh these examinations revealed nothing pathological, reference was not made to them in the case records. When one or several of the above-inentioned examinations were not made, or when some of the findings were pathological, a note was made to this effect.

When, in a few cases, certain special examinations of the urine were made (e.g. Ehrlich’s, Schlesinger’s, Rothera’s and the diazo reaction) the fact was always recorded.

The morphological and certain of the biochemical examinations of the blood (determinations of the alkali reserve, urea, non-protein nitrogen and blood sugar) were carried out a t the clinical labora- tories of the respective hospitals. 01 her biochemical examinat ions were carried out by chemists a t the central laboratories, partly a t UllevAl Hospital and partly a t the Rikshospital.

The ophthalmological examination was in most cases carried out by myself when nothing was said t o the contrary. I tried to carry out these examinations as soon as possible after the patients’ ad- mission to hospital. But it was not always possible to examine a patient on the day of admission as many who had participated in the same carouse were admitted to various hospitals a t the same time. The visual acuily of the patients not given an ophthalmological

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examination before the institution of treatment was determined partly by the patients’ own statements, partly from the report of the doctor in charge. A comparison between the subjective symp- toms and the findings on examination has shown that the patient very soon notices diminution of vision provided he is fully conscious.

When a systematic ophthalmological examination failed to reveal any pathological change, either a report was usually made on the condition of the pupils, fundus oculi and vision alone, or a statement was made that conditions were normal. Vision was stated to be normal when it was 616 and the colour sense was good.

As a rule, when patients were examined during their stay in the medical departments, vision was determined by the best spherical correction. At the first examination in the Eye Department, any astigmatism which might be present was corrected. In the Medical Department, the limits of the field of vision were deter- mined by Donders’ method, whereas a t later examinations, when the patient suffered from amblyopia, the examination was made with a perimeter (radius 300 mm.) and’ Bjerrum’s screen, the dis- tance between the patient and the screen being 1200 mm. When nothing was said to the contrary, a 10 mm object was employed for the examination of the limits of the field of vision and scotoma for white. This examination was carried out in good artificial light or daylight.

In the presence of an absolute central scotoma, it is not possible exactly to make sure that the position of the eye is correct, i.e. that the fixation mark on the periineter and on Bjerrum’s screen lies in the prolongation of the eye’s line of vision. To achieve as correct a position as possible for the eye, care was taken to make sure that the reflexion of a small fiource of light placed on the fixation mark in the arch of the periineter lay in the centre of the cornea or a little inore in the nasal direction.

The approximate size of a scotoma was first determined on the perimeter. At the subsequent examination with Bjerrum’s screen, a white cross was drawn where the crucial point lay in the fixation mark. This cross was a little larger than the scotoma demonstrated. When the patient focusses his eye so that he just perceives the ends of the two limbs of the cross, it may be assumed that the position of the eye is approximately correct.

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The examination of the colour sense was always carried out in daylight. As the patients were, as a rule, tired after the examina- tion in other respects, I did not examine the field of colour vision more than in the two main meridians. On perimeter examination, a 10 mm object was used for determining the limits of the field of vision, and a 5 mm object for the examination of a central scotoma.

When no scotoma could be demonstrated by the aid of coloured objects, the central colour sense was also examined by Ishihara’s test. All the patients with permanent diminution of vision were, with only one exception, kept under observation for some months up l o over three years after the poisoning. All these follow-up examinations were carried out by myself. The course followed by the vision during the first months was in most cases indicated by cur- ves which are more illustrative than words. On the ci!rves, the months are indicated by Roman figures, I for January and so on. The unbroken line represents the vision of the right eye, the broken line that of the left.

Lastly, I would point out that, in calculating the quantity of bicarbonate to be administered a t a given dcgrec of acidosis, I have assumed that the patient weighed 70 kilos. I have followed the same principle in calculating the time taken for the elimination of a given quantity oi ethyl alcohol from the organism.