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98



GENERAL PLAN OF TREATMENT 99

whether due strictly to excessive formation or deficient utihzation is
uncertain. Therefore, in accordance with Naunyn's dictum, acidosis
is present in diabetes whenever an abnormal increase of acetone sub-
stances is demonstrable in the urine or blood. Attempts to replace
this metabohc or biological definition by purely chemical conceptions
of alteration of reaction, derived from experiments in vitro, have
thus far been scientifically fallacious, on grounds which need not be
reviewed here, and clinically are open to the following objections:
(a) these changes represent no independent phenomenon, but only
some late stage of a process which should properly be regarded as a
unit from beginning to end; (6) the striking abnormal production of
acid in the protoplasm, perhaps up to 100 gm. of /3-oxybutyric acid
daily, is the essential disorder to be defined, and the mere neutraliza-
tion of the products by alkali cannot properly be regarded as abolish-
ing this biological acidosis; on the contrary, the necessity of amimonia
formation or alkah dosage to maintain neutral relations should in it-
self be considered evidence of acidosis; (c) the therapeutic point of the
whole matter is that attempts to treat by neutrahzation of products
are often illusory and sometimes dangerous even as temporary meas-
ures, and lead always to failure in the end, while successful treatment
can only consist in stopping the abnormal acid production which is
the essential disturbance.

2. Fasting and Undernutrition Txeatment in Various Types.

The ordinary acidosis of severe diabetes is no contraindication to
beginning a fast, and, as already stated, typically diminishes pro-
gressively during the fast. The more severe the acidosis, and the
more imminent the impending coma, the more urgently is fasting de-
manded, so that the patients of this series who have entered in the
most dangerous condition have been placed immediately on strict
fasting. The results have been favorable, as shown in Chapter VII.

In the milder cases of diabetes, including those previously free from
acidosis, some degree of ketonuria, generally shght, sometimes rather
heavy, may develop during fasting, without danger or any need for
changing the fasting program. Exceptionally, however, in cases in-
herently either mild or severe, blind persistence in fasting may result



100 CHAPTER II

in dangerous or fatal acidosis, as happened in one case (No. 30) in the
present series. This difficulty, though exceptional, is certain to be
encountered if any considerable nimiber of cases are treated; and the
fact that it had not formerly been known is one evidence of the
newness of the fasting method.

This atypical behavior may sometimes be expected in middle-aged
or elderly patients, who have carried their diabetes for possibly 5
to 15 years with little or no apparent harm, whose glycosuria may be
heavy or moderate, whose acidosis may be chronic but slight, and
whose bodily state may be that of good nutrition or slight obesity.
Such a case may appear very promising for quick and gratifying re-
sults. During the fast, glycosuria may persist or diminish; keto-
nuria is generally qualitatively heavy, but quantitatively may not
be great, especially if alkali is not given. What is seen clinically is
first a vague malaise, often with headache or pains elsewhere, dizzi-
ness, and increasing prostration. Nausea seems to be invariable, and
the gravest stage is when vomiting is established. Though the con-
dition is acidosis, the appearance is not that of t3^ical coma.
Dyspnea may not be prominent, and the consciousness may be clear
up to the last hours or minutes of lif^. The end comes with uncon-
trollable vomiting and profound and rapidly progressive weakness.

Treatment in this final stage offers little hope. Glucose or levulose,
orally, rectally, subcutaneously, or intravenously, should theoretically
be most important, provided the diabetes is inherently mild enough to
permit any effective utilization. A few patients elsewhere are said
actually to have been saved by such means. If food can be taken at
all, whatever protein-carbohydirate diet promises to be best retained
is indicated. The use of sodium bicarbonate is customary; it is prob-
ably best given intravenously, possibly by rectum, to avoid nausea.
If carbohydrate or protein as above described succeeds in arresting
the underlying intoxication, it is possible that the cautious use of
bicarbonate may guard against death from simple deficit of alkali
and thus .may be a temporary assistance in tiding over the crisis.
The traditional large doses of alkali are dangerous. If the other
measures fail to arrest the underlying toxic process, alkali, in any
dosage is useless, and the patient dies just as certainly whether the
blood alkalinity is low or high.



GENERAL PLAN OF TEEATMENT 101

The essential treatment lies in prevention, and with simple care
these unnecessary accidents can be avoided. For this purpose, Joslin
has introduced a precautionary program, which, briefly, consists first
in omitting fat from the diet, then gradually diminishing protein and
finally carbohydrate, down to complete fasting unless glycosuria ceases
before. This is opposite to the orthodox treatment of a few years ago,
which started with a gradual reduction of carbohydrate. The plan
is theoretically sound, embodying the same general principle of under-
nutrition which underlies all this treatment. Besides the usual loss
of a little time, there is an imaginable disadvantage in very rare cases,
which might be controllable by immediate fasting but within a few
days might be advanced past hope; also it is a possible question
whether a threatening acidosis may ever be aggravated by food of
any sort, even protein and carbohydrate. The only concrete ob-
servation is in case No. 55 of this series, where it must be confessed
that the diet which made trouble on November 5 did contain an
appreciable quantity of fat. In favor of the gradual procedure are
the following considerations: first, in Joslin's experience, which is
larger than any other, dangers such as here suggested have not actu-
ally been met; second, the duration of the initial fast is shortened;
and third, the occurrence of fasting acidosis has been entirely pre-
vented. This modification has therefore been widely adopted and
will doubtless continue in extensive use. Though Joslin's own cases
are studied by complete laboratory methods, the modified treatment
becomes more important in proportion as laboratory control is lacking.

As already stated, the method of immediate fasting has been em-
ployed in the whole of the present series. Since the early experience
(case No. 30) calling attention to the occasional danger, it has been a
simple matter by combined clinical and chemical observation to avoid
further mishaps. The practical management of dangerous cases of
acidosis may be discussed according to the three classes into which
they fall.

(a) Typical Coma. — ^Patients in actual deep coma generally die.
The considerable proportion of recoveries in this series shows that
treatment is not entirely useless. With coma impending but not yet
complete, death was the usual outcome under former methods, but
under fasting treatment the usual outcome is recovery. It is be-



102 CHAPTER II

lieved that immediate fasting, with the adjuvants mentioned below,
is the safest general rule for cases of threatened coma. Generally the
improvement is quick, and may be evident within twenty-four hours
or less. Sometimes the patient may appear more stuporous on the
second day than on the first, and the blood alkalinity may be almost
stationary or may even fall a little. In all the favorable cases seen,
there has been unmistakable improvement by the third day. It is
worth noting that cases of ordinary coma, coming on in the usual
manner on any kind of diet, have never shown injury from fasting;
i.e., fasting acidosis has not developed where the threatened coma was
due to feeding. The patients whom inexperienced physicians are
likely to be afraid to fast are the ones who usually need fasting most
and who usually show the most striking benefits.

(&) Fasting Acidosis. — ^As stated, occasional patients, in no imme-
diate danger of coma on whatever diet they may be taking, react to
fasting with an increase of acidosis, sometimes to dangerous degree.
The reason for this pecuharity is unknown, and there is also no known
way of foreteUing which cases will exhibit it. Examination of the
case records in this series will show that neither the mildness or severity
or duration of the diabetes, nor the initial degree of acidosis, nor the
intensity or persistance of glycosuria, nor the store of reserve fat
represented by obesity or emaciation, nor the supply of circulating
fat as represented by lipemia, necessarily stands as a determining
factor. The same patient at different times may behave oppositely.
Thus, several cases in this series displayed more or less tendency to
fasting acidosis at first, while at subsequent periods they reacted to
fasting with the usual decrease of acidosis. The essential treatment
for fasting acidosis is food; and the only known rule of procedure up
to the present is if a patient develops acidosis on feeding to fast
him, and if he develops acidosis on fasting to feed him. The kind of
food seems to be of subordinate importance. Thus the fasting acido-
sis symptoms of patient No. 35 ceased entirely on an orthodox protein-
fat diet, which represents the surest means of producing acidosis in
most patients. Nevertheless, it should not be considered that the
choice of diet is immaterial. Fat is theoretically disadvantageous.
Carbohydrate may be beneficial if the diabetes is not too severe, but
should be closely lunited to avoid too great hyperglycemia and gly-



GENERAL PLAN OF TREATMENT 103

cosuria. Protein is on general principles the most valuable food, and
either alone or with such carbohydrate as may seem advisable, it
makes up a low caloric diet which both relieves fasting acidosis and
at the same time continues the benefit of undernutrition. After a
few days of feeding, a second fast is generally well borne, and both
glycosuria and acidosis are brought under control as usual. After
thorough and successful treatment, all patients become able to
undergo fasting without danger from acidosis.

(c) Indistinctly separated from the above two groups are the occa-
sional examples of extraordinary intensity. Some cases of diabetes
almost from the outset, and others after a longer or shorter course of
ordinary symptoms, reach this degree characterized by maximal dex-
trose-nitrogen ratios, enormous protein breakdown, high amino-acid
values in blood and urine, and extremely threatening acidosis. Unless
further improvement in the treatment is devised, probably a majority
of such patients will continue to die, as did several in the literature,
and patient No. 39 in the present series. Some of them apparently
represent a degree of diabetes which is uncontrollable by fasting,
perhaps because fasting is not sufficiently potent to check the rush of
metabolism. There are three favorable considerations in regard to
this condition: first, though famiHar in dogs, it is rare in human pa-
tients; second, it is sometimes controllable by skillful treatment;
and third, a distinction exists between intensity and severity, for
if it is possible to weather the immediate storm of symptoms, these
extremely intense cases sometimes turn out later to be less severe
than anticipated. Thus, the patient of Geyelin and DuBois gained
a tolerance running into hundreds of grams of carbohydrate, and the
patient of Jonas and Pepper seemingly recovered from his diabetes
altogether. In Chapter VIII it is shown that the distinction rests
upon the apparently functional nature of the chief disturbance un-
derl3dng the intense symptoms, while anatomic destruction of the
islands of Langerhans, which is the fundamental basis of true severity,
has not necessarily advanced very far in these cases. As regards
acidosis, it may be assumed as a general principle that if fasting does
not control glycosuria the result will be coma. These cases differ from
those of group (b), which somehow react unfavorably to fasting irre-
spective of the presence or absence of glycosuria. The fatal acidosis



104 CHAPTER n

from prolonged fasting in the present group seems to occur only be-
cause of the persistence of high glycosuria. Successful treatment has
consisted in replacing fasting by an undernutrition diet of carbo-
hydrate or protein. Carbohydrate may be helpful for diuresis, but
with a maximal D:N ratio its value otherwise is questionable.
Protein offers theoretically the greatest advantages, in that it fur-
nishes carbohydrate and urea for diuresis and ammonia for neutral-
izing acids, and at the same time is the most important food for
maintaining strength and protecting body nitrogen. Successful
treatment with carbohydrate and protein is illustrated by the cases
of Geyelin and DuBois and Jonas and Pepper above mentioned.
Success with pure protein diet is illustrated by case No. 37 in this
series. This boy had first entered the hospital with impending coma
which had developed on a mixed diet and which cleared up smoothly
on fasting. In a relapse 11 months later, he was readmitted with gly-
cosuria which had resisted 8 days of fasting and acidosis which
threatened early coma if fasting were continued. By a practically
pure protein diet for 10 days, the acidosis and other symptoms were
relieved, and then glycosuria was easily abolished by fasting. As
mentioned, in some cases fasting, feeding, alkali, and all other measures
are unavailing, and here death occurs from acidosis or exhaustion
within a few days. Obviously, all cases of this group should be under
the care of the most experienced specialist available.

3. Adjuvant Measures and Remarks.

(o) Emptying Alimentary Canal. — ^When it is known that food has
been recently eaten, lavage of the stomach is advisable in impending
coma, and if there is any doubt, it is a wise precautionary measure.
Joslin makes it a routine for children with dangerous acidosis. It is
also important to empty the intestine thoroughly by a combination
of any vigorous purgative and high colonic irrigation. There may be
some incidental benefit from absorption of saline solution if this is
used for the colonic injections, or of. alkali if the irrigation is per-
formed with sodimn bicarbonate solution. Case No. 25 illustrates
the great difl&culty of securing adequate intestinal evacuation in some
instances, and also its importance.



GENERAL PLAN OF TREATMENT 105

(b) Drugs. — Except in accidental emergencies, it is doubtful if drugs
ever rescue patients from acidosis. Such an emergency is shown in
case No. 11. This patient was not actually saved; but if there is
cardiac and renal failure along with acidosis, it is evidently possible
that life may be preserved by medicines which restore circulation and
excretion. When any patient is sinking into. the stupor of ordinary
coma or the weakness of fasting acidosis, there is always the incli-
nation to stimulate heart, brain, and kidneys by such drugs as caf-
feine and digitalis, if only in the hope of supporting strength until
other measures have time to take effect. The liberal use of coffee, as
illustrated in a few cases in this series, may be of some slight service.
But whether employed early or late, drugs are probably never able to
change the result in uncomplicated cases. • If a large dose of alkali is
given intravenously, there is a possible question whether some circu-
latory stimulant might be of value for guarding against the sudden
death which sometimes follows within a few hours.

(c) Sugars. — Glucose and levulose have received long and extensive
trial as weapons against acidosis in the past. Their promise of use-
fulness is greatest in fasting acidosis, at the stage when all ordinary
food is vomited. They may then be given, preferably in 5 per cent
solution, rectally, subcutaneously, or intravenously. For the latter
purpose, a slow continuous infusion by some such device as that of
Woodyatt' appears obviously best. For ordinary coma, sugar might
have some value as a diuretic, and also for diminishing the formation
of acetone bodies if it can be burned. But as a rule, the blood sugar
is already undesirably high, and little if any sugar can be metab-
olized. It is well known that the attempted sugar treatment of coma
has in general been such a failure that it has been abandoned by the
best authorities. Von Noorden^" found absolute fasting more effective
than levulose, milk, or oatmeal for coma. Anything that aggravates
the diabetes and delays the clearing up of glycosuria may possibly
act injuriously also upon the acidosis. For these reasons it is be-
lieved that as a rule sugar or carbohydrate should not be used for the
treatment of ordinary cases of acidosis.

' Woodyatt, /. Biol. Chew,., 1917, xxix, 355-365.
'" von Noorden, C, Zuckerkrankheit, 1912, 388.



106 CHAPTER n

{d) Alcohol. — So far as observable empirically, alcohol has shown
no specific value in connection with acidosis. Some experiments to be
published later agree with the finding of Higgins, Peabody, and Fitz"
that it tends rather to increase acidosis. One objectionable feature
is its frequent nauseating effect. For these reasons, the use of
alcohol is considered inadvisable even for weak patients with serious
acidosis.

(e) Salts. — The value of inorganic salts and the danger of extreme
loss of salt have been emphasized especially by Joslin. Sodium
chloride is valuable as a diuretic; also, its retention is associated with
edema, and only one patient with edema in Joslin's experience has
ever died in diabetic coma. Therefore sodium chloride may be ad-
ministered by mouth in quantities up to 20 or 30 gin. daily unless
prevented by nausea or other contraindication; physiological saline
solution also is useful, by rectum, subcutaneously, or intravenously,
for conveying salt as well as fluid. In case No. 1 and a few others,
trial was made of giving also salts of potassium, calcium, and mag-
nesium, with a view to physiological balance, but no apparent advan-
tage has been found in this plan over the use of sodium salts alone.
Soup is valuable partly for the salts it contains.

(f) Fluids. — As already mentioned, the conduct of fasting with
ordinary moderate acidosis calls for only moderate quaritities of
hquids. On the other hand, the largest practicable fluid supply is
one of the most essential matters in the treatment of threatened
coma. Authorities from Rumpf to Joslin have recognized the
danger of desiccation of the body, especially with the vomiting which
occurs so frequently. The further use of fluids is to promote the
freest possible diuresis. Joslin set the standard of 10 liters a day
when possible. If the patient can drink and retain sufficient liquid,
it need not be given in other ways. The patient should be persuaded
to take water as much and as often as possible, either hot or cold, and
free use should also be made of coffee, tea, soup, cracked ice, or what-
ever else will aid in introducing fluid and perhaps also in preventing
nausea. If drinking is insufficient — for example, if an adult with im-
pending coma cannot retain 5 liters per day — recourse may be had to

" Higgins, H. L., Peabody, F. W., and Fitz, R., /. Med. Research, 1916, xxxiv.
263-272.



GENERAL PLAN OF TREATMENT 107

corresponding quantities of 0.85 per cent sodium chloride solution by
rectum, subcutaneously, or intravenously. From 500 to 1000 cc.
salt solution at a dose intravenously is considered by Joslin often
preferable to alkali, because less dangerous. Here again the Wood-
yatt injection apparatus might be advantageous. The reasons for
the importance of keeping up copious diur-esis by fliiids are the fol-
lowing. First, the possible concentration of acetone bodies in the
urine is limited (the highest observed by Fitz was between 9 and 10
gm. per liter); for this reason the excretion can often be multipHed
by almost as much as the quantity of urine is multiplied, and large
quantities of dangerous material thus removed. A high excretion,
e.g. 50 gm. or more of total acetone bodies daily, is never possible ex-
cept with abundant diuresis. Second, /3-oxybutyric and acetoacetic
acids circulate in the blood only in the form of salts. They are partly
eliminated as salts, but also to an important extent the kidney saves
the base for the body and excretes the free acids. Through this saving
of base by the acid-secreting power of the kidney, the administration
of fluid is equivalent in some degree to the administration of alkali,
without the special disadvantages or dangers of the latter.. .

(g) Laboratory Guidance. — Mention has already been made of the
various routine tests for acidosis, and preference expressed for the
Van Slyke plasma bicarbonate method. More reliance can be
placed upon the blood alkalinity, determined by this or by one
of the less direct methods, than upon any other single feature of the
condition, and without this information it is often impossible in
critical cases to judge progress or direct treatment intelligently.
With any serious degree of acidosis, estimation of the bicarbonate
reserve should be made once daily. In acute danger, such analyses
are sometimes demanded at frequent intervals, perhaps once every 4
hours, to indicate whether the response to treatment is favorable or
whether a change should be made. At this stage, the greatest service
of this test is to give warning of an increase of acidosis on fasting,
often before clinical symptoms make this evident, and in time to avert
the danger by giving food. As an arbitrary ground plan for apply-
ing the results of this test, the scheme in Table I may be suggested.
Nevertheless, clinical judgment and experience are important in
deciding whether unfavorable progress calls for a reversal of treatment



108



CHAPTER II



or for more rigorous adherence to the same plan. There is ample
evidence in the present series of cases that neither this nor any other
single test can be followed blindly as an infallible guide. Irregularities
are sometimes marked, even in absence of extraneous modif)dng factors.
Thus, patient No. 63 showed the lowest CO2 capacity in the entire
series (12.3 per cent), yet recovered promptly, whereas other patients
died although their bicarbonate reserve was by no means so low.
Patient No. 35 developed malaise, nausea, and drowsiness on fasting,
and the observers were convinced that unless fed he would have died
in the typical intoxication. The CO2 capacity was within normal
limits even without alkah dosage. Probably it would have fallen
at a later stage; but the significant facts are that the clinical symp-
toms alone gave warning in time to permit effective treatment, that

TABLE I.



Degree of acidosis.


Plasma COj.


Further drop of COz pennitted before interrupting fast.




vol. per cent







Above 53 .


To 45 volume per cent.


Mild.


53-40


Drop of 10 to 5 volume per cent.


Moderately severe.


40-31


(t (c 3 <( 2 " " "


Severe.


Below 31.


Fast interrupted in 6 to 12 hrs. unless CO2 rises
with fasting and alkali.



theintoxication symptoms increased when sodiumbicarbonateproduced
an actual rise in the CO2 curve, and that feeding cleared up the sjonp-
toms even though the CO2 capacity was slightly lower on certain subse-
quent days than at the time of the intoxication. Such discrepancies and
irregularities, spontaneous in origin, are much less numerous than those
resulting from alkaU therapy. Thus in case No. 30, a typical ex-
ample of acidosis with fatal result on fasting, the plasma bicarbonate
was forced up within normal limits by alkali dosage while well marked
intoxication was present, and the last reading, with severe and hope-
less intoxication existing, was 45 per cent, which falls within the limits
of "mild" acidosis according to the above table. Patient No. 45
had before admission been kept saturated with huge doses of sodium
bicarbonate. He' entered almost in coma, typical except, for absence
of hyperpnea, notwithstanding the CO2 capacity of 73.5 volume



GENERAL PLAN OF TREATMENT 109

per cent in his plasma. In full coma on September 9, the CO2 ca-
pacity was 84.9 volume per cent, i.e. abnormally high, and higher than
on other occasions without coma. Patient No. 71 was received in



Online LibraryFrederick M. (Frederick Madison) AllenTotal dietary regulation in the treatment of diabetes → online text (page 11 of 76)