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coma with the usual low plasma bicarbonate of 22.1 per cent. On
the subsequent days he remained intoxicated and delirious, even
when the plasma bicarbonate was forced as high as 50.2 per cent,
which is near the normal level for a boy of 9 years. Thereafter it
was never below 38.8 per cent, and on the day of death in coma was
48.5 per cent. Patients not in this series have also been seen, who
died in coma notwithstanding normal CO2 capacity of the plasma.
These facts cast no reflection upon the accuracy of the analytical
method, but merely illustrate that dearth of alkali is not the sole nor
essential feature of the condition. Fasting is sometimes beneficial
even when the blood alkalinity falls somewhat; but in particular, a
high alkalinity is no a:ssurance of safety in the presence of obvious
chnical intoxication or a high and increasing concentration of acetone
bodies in the blood.

(h) Alkali Therapy. — This subject is partly discussed in connection
with the results of the treatment of coma, in Chapter VII. The pos-
sible benefits consist in relieving a dangerous dearth of alkali, and in
facilitating the elimination of acetone bodies. The possible harm lies
chiefly in the nausea which may result from oral administration and
the sudden death which may follow within a few hours after excessive
intravenous doses. It is conceivable that alkali may affect the toxic
state for either good or ill in ways not now understood. Both bene-
ficial and injurious effects are illustrated in the present series of
cases.

Close observation also shows that, whether the differences are sig-
nificant or accidental, the condition called diabetic coma does not
present a uniform picture. Aside from the rather atypical fasting
form, there are differences in the symptoms which usher in coma. At
one extreme are patients with extreme dyspnea, gasping so that
speaking and swallowing are difficult, yet with consciousness perfectly
clear until near the end. Such air-hunger is accounted for largely
though not entirely by acid intoxication, and alkali may perhaps save
life. Of patients of this tj^e, No. 63 was saved by alkali even after
he had gone on into unconsciousness, when he might not have been



no CHAPTER n

saved by simple fastingj^ the dyspnea of No. 39 was somewhat re-
lieved by alkali, but nevertheless she went on into stupor and died.
At the other extreme are cases characterized chiefly by malaise,
drunkenness, and drowsiness, with hyperpnea little marked; and these
prodromal symptoms may also be relieved by alkali, sometimes with
surprising promptness. The great majority of cases represent a
mixture falling between these two extremes."

The older clinical literature seems to prove that many patients with
continuous ketonuria were saved from both dyspnea and intoxication
for considerable periods by alkaU, and the onset of coma thus de-
layed. In the treatment of actual coma, alkaH has been seldom
successful, and the patients saved by it are few. Under all circum-
stances, its effect is necessarily temporary and palliative. The fact
is well known that the death rate from coma was not appreciably
altered by the introduction of the alkali treatment. If death was
somewhat deferred, the patient died subsequently in coma neverthe-
less. Magnus-Levy recognized that this result could be prevented
only by some method which would check the process of acetone body
production. Fasting checks this process; accordingly the great ma-
jority of cases of acidosis can be treated by this means alone, and
alkali holds no more than a minor adjuvant position. Its use has
seemed valuable under two conditions. The first is in combating a
long and stubborn acidosis, as in patient No. 23, both for relieving
malaise due to acidosis and for avoiding more serious danger. Ex-
perience does not prove whether it is best given in smaller doses, 5
or 10 gm. daily, for longer periods, or in larger doses on occasional
days when demanded by clinical or laboratory indications. Such a
need is rather rare, and the indiscriminate or routine use of alkali
is not to be recommended. Particularly prolonged administration,
of 2 weeks or more continuously, is probably best avoided, for fear of
harm in some patients. The second use of alkali has been for com-
bating coma in certain cases as already mentioned. Under all cir-
cumstances, it must be understood that control of the metabolic
condition by fasting or food is the essential means of treatment;

"^^This was written before reading the closely similar observations of Cam-
midge, Am. Med., 1916, xxii, 363-373, who suggests that one form is due to loss
of blood alkaU, the other to loss of tissue alkali.



GENERAL PLAN OF TREATMENT



HI



failure in this attempt must end fatally in spite of any dosage of
alkali, and the crisis is not past until the production of acetone bodies
is markedly and progressively diminishing.

In any of the three types of acidosis above described, continuously
high or increasing ketonemia and intoxication lead sooner or later
to a condition where the further administration of alkali is ineffec-
tual. The reason for the failure is unknown, because the real nature
of the intoxication is unknown. The possible irregularities in the
ketonemia and the alkaline reserve are indicated by observations of
Fitz'^ upon three fatal cases of coma (Table II).

TABLE II.





1st observation


, in early coma.


Interval
between 1st

and 2nd
observations.


Sodium
bicarbonate
by mouth
in interval.


2nd observation shortly before
death in coma.


Case No.


CO2 capacity
of plasma.


Total acetone

bodies of plasma

(as acetone)

per 100 cc.


CO2 capacity
of plasma.


Total acetone

bodies of plasma

(as acetone)

per 100 cc.


72 ■

71


sol. per cent
18.9
14.0
22.1


mg.

71.2 .

54.5
83.8


35 hrs.
8 "
8 days


gm.



25

72


per cent
26.7
17.0

48.5


mg.
127

97.8
192.5



By reference to the history of case No. 71, it will further be seen
that during 4 days before the final observation, the CO2 capacity
of the plasma ranged from 38.8 to 50.2 per cent, and the total acetone
of the plasma between 212.5 and 368.4 mg. per 100 cc. Also, there
was no constant relation between plasma alkali and plasma acetone.
These cases afford additional illustrations of increasing intoxication
and death notwithstanding rising alkaline reserve of the plasma.
Still other examples might be gathered from the literature to show
that the intoxication is by no means in proportion to the concentration
of total acetone in the plasma. Hence the failure of alkaU is not
necessarily an insufficiency of diuresis resulting in retention of these
acids or their salts. There is no evidence that alkali either increased
or diminished the production or accumulation of acetone bodies at
this stage. This point deserves further investigation. The sugges-

'^ Fitz, R.. Acetone Bodies in the Blood in Diabetes, Tr. Assn. Am. Phys., 1917,
xxxii, 155-158.



112 CHAPTER n

tion, especially of recent English authors," that the explanation hes
in different relative proportions of acetoacetic and hydroxybutyric
acids, the one being more toxic than the other, lacks proof at present.
There is need of more clinical observations and animal experiments
also on this question. In fact, nothing more than a descriptive status
is really estabhshed even for the word "intoxication." Diabetic coma
is a profound breakdown of metabolism. It may well be, in accord
with Woodyatt's ideas, that the abnormality extends through the
whole chain of intermediary compounds, that no one substance will
be demonstrable in lethal quantity and toxicity, but that the general
disorder of protoplasmic chemistry may be responsible for death.
Alkali could necessarily have little influence here. Certainly the con-
dition is complex. Ketonuria, ketonemia, lowered plasma alkalinity,
and clinical symptoms are ordinarily associated in a relation regarded
as t)^ical. The abnormahties of kidney function with severe acidosis
are notorious; they presumably involve variable excretion of acids and
bases; they necessarily upset any calculations based on normal renal
activity; and they may explain more or less of the exceptional behavior
noted. Aside from the occasional spontaneous variations, it is ob-
viously possible to distort the usual relations by artificial alteration of
one feature, for example raising the blood alkali by administration of
alkali, without altering the underlying process or the clinical result.
For practical purposes, sodium bicarbonate is the alkali of choice,
on the basis of effectiveness and innocuousness. A salt of strongly
alkahne reaction, such as sodium carbonate, deranges the stomach
more readily, and its intravenous use involves greater danger of
thrombosis in veins'^ or, in case of leakage, necrosis about them.
Stronger alkalies must be changed immediately into sodium bicarbon-
ate in the circulation, by chemical laws and because an actually alka-
line reaction of the blood would be incompatible with Kfe. This fact
does not necessarily conflict with Murlin's" observation of a differ-
ence in the action of sodiimi carbonate and bicarbonate upon experi-

1* Cf. Hurtley, W. H., Quart. J. Med., 1916, ix, 301-408. Kennaway, E. L.
Biochem. J., 1914, viii, 355-365.

" Cf. Umber, Deutsch. med. Woch., 1912, xxxviii, 1403.

" Murlin, J. R., and Sweet, J. E., /. Biol. Chem., 1916-17, xxviii, 261-288.
Murlin, J. R., and Graver, L. F., Ibid., 289-314.



GENERAL PLAN OF TREATMENT 113

mental animals; but no superiority of strong alkalies in the practical
treatment of human cases has been established. Any special advan-
tages in the use of other bases (potassium, calcium, magnesium) have
also not as yet been demonstrated.

Sodium bicarbonate can be given by the four usual routes.

By Mouth. — This method is preferred when possible. The maxi-
mar dosage is generally 2 or 3 gm. an hour or 5 gm. every 2 hours.
Few patients can take 100 gm. per day, and none can take this for
many days in succession. If the taste is objectionable, it is prob-
ably best disguised by administering in carbonated water. The
most serious objection to the oral method is the possible nausea,
and the dosage should be regulated to avoid this. Diarrhea is also
frequent. More or less edema, generally harmless, may result from large
doses. Defective or sensitive kidneys may possibly suffer injury, and
inhibition of diuresis is a possible serious consequence. On the whole,
this method is the safest and with prudence seldom results in harm.

By Rectum. — The well known drop method is the best. In deep
coma, retention and absorption are generally poor. In a less extreme
stage, this method may be the safest and most convenient substitute
or supplement for oral administration. A mixture of equal parts of
physiological saline and 4 per cent sodium bicarbonate solution (mak-
ing a 2 per cent bicarbonate) was recently given thus to a boy of 12
years for 4 days continuously, and as much as 35 gm. sodium bicar-
bonate and corresponding quantities of fluid were thus introduced
without the least difficulty or irritation. There is a possible question
whether, if the large bowel is filled with injection fluid, there may be
any effect on peristalsis higher up which will aggravate vomiting or
interfere with dosage by stomach. Otherwise there is probably no
objection to giving alkali by rectum.

Intravenously. -^Th.e usual fluid for injection is 4 per cent sodium bi-
carbonate in water or salt solution. Followers of Martin Fischer favor
hypertonic solutions, for withdrawing water from the tissues and for
promoting diuresis. Intravenous alkali injections, instead of being
among the first measures employed, should be resorted to only
reluctantly and on urgent necessity. The possible danger of the
familiar practice of injecting a liter of 4 per cent bicarbonate solution
has already been mentioned. The occasional sudden reviving effect



114 CHAPTER n

is probably due to a circulatory influence of the bicarbonate or the
fluid or both. It is ahnost always temporary, and perhaps carries
in itself the danger of later collapse. There are times when not
enough alkali can be given by stomach or rectum to prevent a danger-
ous fall in blood alkalinity. The intravenous method is then com-
monly used, but the quantities are probably most safely limited to
about 250 cc. for adults, repeated at intervals of several hours if neces-
sary. Presimiably the Woodyatt apparatus for continuous imiform
injection would be best of all. Intravenous alkali injections should be
used to keep the blood alkaU from falling too dangerously low, rather
than to try to maintain it at a normal level, but sometimes remark-
ably large quantities are required even for the former purpose. The
largest doses may be demanded especially in the severest intoxication,
which is the very time when, owing to feeble circulation, the danger
is greatest.

Since boiling changes bicarbonate into the carbonate, solutions
may be prepared in one of the following three ways: (1) by boiling the
solution, and then passing sterile CO2 gas through it to change car-
bonate back to bicarbonate, until a pink color is no longer obtained
in samples tested with phenoIphthalein;i' (2) by making the solution
without boiling, sterilizing it by filtration through porcelain; (3) by
taking clean sodium bicarbonate, preferably from a freshly opened
package of a chemically pure brand, with sterile apparatus into sterile
water or salt solution, without further sterilization." This last and
easiest method is safe enough for intravenous and perhaps even for
subcutaneous use. Solid particles are removed by filtration through
sterile cotton or filter paper if necessary. Solutions are wanned to
body temperature before injection.

Subcutaneously. — Magnus-Levy" called attention to the fact that
sodium bicarbonate, as a neutral salt without marked irritating prop-
erties, can be given subcutaneously. The method is relatively little
employed, because of the fear of infecting or damaging the susceptible
tissues of a diabetic, as well as producing pain or discomfort. One
feature of usefulness was demonstrated in the twelve year old boy

" Magnus-Levy, A., Ueber subkutane Infusionen von Mononatriumkarbonat,
Therap. Monatsh., 1913, xxvii, 838-843. Also Joslin's text, 1917, 397.



GENERAL PLAN OF TREATMENT 115

above mentioned. On his last day of life, 35 gm. sodium bicarbonate
given by rectum were only partly absorbed. 40 gm. given intraven-
ously failed to check the fall of the alkaUne reserve. The patient
was sinking into unconsciousness, with Kussmaul breathing and the
full picture of typical diabetic coma; CO2 capacity of plasma 26.5
volume per cent. A total of 90 gm. sodium bicarbonate in 4 per
cent solution was given subcutaneously between 7 :30 p.m. and mid-
night. The hyperpnea was considerably diminished; there was no
perceptible influence upon consciousness or the general condition for
either good or ill. The slow increase of intoxication continued as
before. Death occurred at 1:40 a.m., and blood taken immediately
after showed a plasma bicarbonate reading of 68.1 volume per cent.
A few authors heretofore have opposed the acid intoxication hy-
pothesis by reporting death in coma with alkaline urine. Inability
to give enough alkali has been a prevalent excuse for failure. There
is no objection to placing enough bicarbonate beneath the skin to
give the patient the benefit of any desired level of alkalinity; and
with the aid of the recent improved methods of estimating the alka-
line reserve, it is possible for any follower of the acid intoxication doc-
trine to convince himself that the patient's blood alkali can be kept
at a fully normal level, but he dies in deep coma nevertheless.

B. Infectious and Surgical Complications and Emergencies.

The methods employed in managing cases of this group are shown
in the individual histories, and the collective results are presented
in Chapter VII. The experience, though favorable on the whole, is
so limited that discussion of the treatment must be based largely on
the literature and on general principles. For the older literature,
reference may be made to text-books and the papers of Umber,i'
Kaposi,!' Kraus,^" and Karewski;^! and for developments under the
newer dietetic methods, to JosUn's text and Strouse's^^ paper. Com-

^* Umber, Deutsch. med. Woch., 1912, xxxviii, 1401-1403, 1433-1434.
" Kaposi, H., Ergebn. Chir., 1913, vi, 52-75 (128 references to literature).
^^ Kraus, F., Deutsch. med. Woch., 1914, xl, 3-8 (with statements by Naunyn,
von Noorden, and Minkowski).
^iKarewski, F., Deutsch. med. Woch., 1914, xl, 8-13.
22 Strouse, S., Med. Clin. Chicago, 1916, ii, 37-52.



116 CHAPTER n

plete discussion of surgical complications, like complete treatment of a
patient, demands the collaboration of physician and surgeon. The
present brief suggestions will omit statistics, most surgical details
and finer classifications, and will be limited to general outHnes of
practical procedure.

Certain broad dicta may be taken directly from former authors.
First, every patient coming for treatment of any medical or surgical
ailment should have the urine tested for sugar, whether diabetes is
suspected or not. There is ample proof that this admonition is far
from superfluous even today. Even with a negative test, Kaposi
urges strict inquiry for diabetes in the family or past history, and
attention to present or past obesity, suppurations, or other sus-
picious indications. Second, mildness of the diabetes and slightness
of the complication or operation promise the best outcome and the
least contraindication to surgical measures; but mild diabetes may
turn suddenly severe with a complication or shock, and a complica-
tion may be aggravated by diabetes, so that unnecessary interference
should be avoided in the presence of any active symptoms, and the
prognosis should always be guarded. The more threatening the
comphcation and the more critical the necessity of surgical inter-
vention, the less is diabetes regarded as a contraindication. Third,
the special dangers threatening the diabetic are peculiar susceptibility
to infection, subnormal healing and repairing power, and acidosis.
The last causes most deaths. The first two are largely overcome by
aseptic and operative care. Fourth, the better the dietetic prepara-
tion, the less the danger. Since acidosis is the chief peril, the best
preparation will include a maximum assimilation of carbohydrate;
therefore formerly ap oatmeal period was recommended (von Noor-
den, Addis, and others).^' Fifth, the surgical technique of an emer-
gency operation should be the simplest yet most effective possible,
avoiding shock, traumatism or long anemia of the parts, elaborate-
ness, and anything tending to lengthen the time of operation or
dispose to subsequent sloughing or infection. Sixth, local or spinal
anesthesia is considered safest from the standpoint of acidosis.
Proper general anesthesia is usually well borne by well prepared

23 Addis, T., J. Am. Med. Assn., 1915, Ixiv, 1130-1134.



GENERAL PLAN OF TREATMENT 117

patients. It should be as brief as possible. Psychic as well as
physical distress should be guarded against. The anesthetic of
choice is nitrous oxide and oxygen. Ether is more dangerous.
Chloroform should never be used for diabetics. Seventh, postopera-
tive care includes on the one hand the most skilled dieting, aiming
particularly at carbohydrate assimilation, and on the other hand sur-
gical precautions, such as exercise and other measures favoring cir-
culation and general hygiene, and avoidance of tight dressings.
Eighth, fatal coma or other disaster may occur from any sort of
operation, in any grade of diabetes, after any form of preparation,
any kind of anesthetic, and any postoperative care (Naunyn, Karew-
ski, and others). Ninth, operative relief from tumors or other
troubles sometimes has a beneficial influence upon the diabetes
(Eising and others).^ Tenth, the use of alkali stands on about the
same basis as in uncomplicated cases. The frequent occurrence of
acidosis with operation or anesthesia in non-diabetics has been brought
into some prominence of late (Crile,^^ Bradner and Reimann,*^ Bum-
ham,*' Lincoln,^' Morriss,*' and others). The recent work of Hen-
derson and Haggard^" indicates that the lowering of the carbon
dioxide capacity of the plasma does not represent a true acidosis.
Accordingly, only the acetone body production can here be regarded
as evidence of acidosis. The treatment has consisted in preliminary
carbohydrate diet, and, in emergency, glucose and sodium bicarbon-
ate, alone or separately, orally, rectally, subcutaneously, or intra-
venously. The glucose is unquestionably the more important for a
non-diabetic. The value of alkali has been questioned. Naunyn
strongly advocated saturating every diabetic with sodium bicarbon-
ate before operation, and he has had the largest following. Undoubt-
edly the blood alkahnity can be raised by alkali dosage, but there is
the open question whether artificially raising the blood alkalinity is

2* Eising, E. H., /. Am. Med. Assn., 1914, Ixii, 1244-1245.
" Crile, G. W., Ann. Surg., 1915, Ixii, 257-»-263; ^w. Med., 1916, xxii, 447^51.
2^ Bradner, M. R., and Reimann, S. P., Am. J. Med. Sc, 1915, cl, 727-733.
"Burnham, A. C, Am. Med., 1916, xxii, 438-441.

28 Lincoln, W. A., Ann. Surg., 1917, Ixv, 135-141.

29 Morriss, W. H., /. Am. Med. Assn., 1917, Ixviii, 1391-1394.

5" Henderson, Y., and Haggard, H. W., J. Biol. Chem., 1918, xxxiii, 333-371.



118 CHAPTER II

necessarily synon37inous with benefiting the patient. Alkali has not
prevented the high mortahty from postoperative acidosis in the past,
Strouse has had good results in operations with alkali, and Joslin
in operations without alkaU. The practitioner's choice in individual
cases will be governed by his attitude on the general subject.

Contrary to past practice, alcohol is at present not used in this
hospital as a food at any stage in diabetic complications or the
acidosis accompanying them.

Authors have divided complications into those for which the diabetes
is wholly or partly responsible, and those independent of the diabetes.
Therapeutic measures are sometimes influenced by theories as to the
reason why diabetics are subject to so many characteristic compli-
cations and so lacking in resistance to damage of all kinds. Notions
that excess of sugar directly injures tissues or provides a favorable
medium for bacteria have been sufficiently discredited. It is also
important to emphasize that thougli malnutrition predisposes to in-
fection, the susceptibility of diabetics is something special and
peculiar, since hunian beings or animals suffering from other condi-
tions involving equal or greater inanition and cachexia are not
afflicted in this manner or degree. As formerly pointed out," one
general conception of diabetes is apphcable also to all complications.
The present treatment is built upon the idea, supported by consid-
erable evidence in addition to the treatment, that diabetes is weak-
ness of the general nutritive function, including both cataboUsm and
anaboHsm. It is thoroughly in line with this poin^ of view that every
part of the diabetic body should manifest diminished power of main-
taining normal function, of repairing the natural wear and tear, of
healing wounds, and of resisting infectious invasions. Not only the
grosser complications, but also retinitis, cataract, arteriosclerosis,
neuritis, asthenia out of proportion to loss of flesh, and the multitude
of other disorders listed in classical text-books, accord with this con-
ception. Since the trouble is due to deficiency not of nutritive ma-
terials but of the nutritive function, relief should be expected from
strengthening this function, even at the price of dimmished food supply
and body weight. Experience indicates that this result actually

«i Men, Am. J. Med. Sc, 1917, cliii, 313-371.



GENERAL PLAN OF TREATMENT 119

follows, and that there should be no hesitation to impose rational un-
dernutrition for the purpose of raising resistance.

Complications and operations fall for practical management into
those with which there is opportunity for preparation, and those
affording no opportunity for preparation.

1. When There is Time for Preparation.

(a) Prophylaxis. — ^Just as the food tolerance is never fully restored
in typical diabetes, so also the Resistance is probably never entirely
normal. It is possible, for example, that no dietetic treatment will



Online LibraryFrederick M. (Frederick Madison) AllenTotal dietary regulation in the treatment of diabetes → online text (page 12 of 76)