A Study of Blood Sugar Levels in Eclampsia

MAYS-MCCORD:

405

BLOOD Sl'GAH U :YEL:-,1 J);' f:t'J,AMPSIA

REFERENCES

(1) Swanson, W. W.: J. Biol. Chern. 62: 565, 1925. (2) Quick, A. J.: Am. J . Med. Sc. 185: 630, 1933. ( 3) Stander, H. J.: Medicine 8: 1, 1929. ( 4) Cross, R. C.: AM. J. OBST. & GYNEC. 18: 800, 1929. (5) Sullivan, C. F., .Z'ew, W. P., and Watson, E. M.: J. Obst. &1 Gynec. Brit. Emp. 41: 347, 1934. (6) Griffith, W. H.: J. Biol. Chem. 66: 671, 1925. (7) Swick, M.: Surg. Gynee. Obst. 56: 62, 1933. (8) Kings· bury, F. B., and Swanson, W . W.: Arch. Int. Med. 28: 220, 1921. (9) Bryan, A. W.: J . Clin. Investigation 2: 1, 1925. (10) Morgulis, S., Pratt, G. P., and Jahr, H. M .: Arch. Int. Med. 31: 116, 1923. (11) Johnston, C.: J. Clin. Investigation 9: 555, 1931. (12) Quick, A. J.: M . Clin. North America 17: 1325, 1934. (13) Quick, A. J.: J. Bioi. Chern. 92: 65, 1931. (14) Quick, A . J . : ;r. Bioi. Chern. 98: 1.'i7, 1932.

A STUDY OF BLOOD SUGAR LEVELS IN ECLAMPSIA C. R.

MAYs, M.D., AND

W. M. McCoao,

PH.D ., XEw ORLEANs,

(From the Departmemts of GyneeololJy o:nd Biochemistry Lo-uisio.na State Medi<>al Center and the State Clw.rity Ho sz1ital. )

LA.

lJwi7•Pr.~ity

RECENT articles on the treatment of eclampsia there appears an INincreasing use of dextrose in the treatment of pregnancy toxicosis. There still exists, however, some controversy on the rationale of this therapeutic procedure. Various methods of administration and doses

Period 1

Fig. 1.-Case 1. Time 1 hr. 30 min.

Samples taken at thirty-minute intervals. Sugar Cone. Convulsions Av. Fall 258.0 mg. per hr.

have been recommended based upon a variety of theories regarding the beneficial effects of dextrose infusions. For this reason we have studied the influence of blood sugar concentration on the incidence of convulsive manifestation of eclampsia. We have favored the use of dextrose in the treatment of our eclamptic patients for its protective influence against liver degeneration and the strong diuretic effect it produces. The diuretic {'fficiency of dex-

406

AMERICAN JOURNAl, OF OBSTE'l'RICS AND GYNECOLOGY

trose must be directly proportional to the molecular concentration that it reaches in the circulating blood and the duration of time that is held at this given high level. In the selection of cases for this study only those patients which showed convulsive manifestations of eclampsia, immediately preceding the period of observation were employed. Medication, other than

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P e riod 1

2

tlliii\S

+

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F ig. 2.-Case 2. Samples t aken at thirty-minute inter vals. Time Av. Fall Conv uls ions Sugar Cone. 1 hr. 43 min. 21. 5 mg. pe r hr. 1 a t 122 mg. % 50 min . 222.0 mg. per hr. 1 a t 260 mg.%

1011

It

' +

Period 1

Fig. 3.-Ca.se 3. Time 1 hr. 30 min.

Sam pl s tak e n at thirty-minute Intervals. Av. Fall Convul sions 1 24.0 mg. per hr.

ugar Cone.

insulin and glucose, was not administered during the experimental period except in three cases, a notation of which is made in thB case report. During the earlier studies (Cases 1, 2, 3, 4, and 6) the blood sugar determinations were made upon capillary blood fl'Om the finger tips by the method of Folin and Malmros.I In the remainder of the series blood was ohtained from the median vein and preserved in tube~ containing oxalate and fl.oride 2 in the ice box until analyzed eight or ten hours afterward at the latest. The blood proteins were precipitated according to Somogyi3 and th e sugar determined by the method of Folin.4

MAYS-:MC CORD:

BLOOD SlTnAR J..IWELS Jl\' Et'LA:MPSIA

-lOi

RESULTS

In 'fable I is presented the blood sugar concentrations at the beginning of the study. Our data are presented in Figs. 1 to L4. Analysis of these charts may be found in 'fable II.

Period 1

Fig. 4.-Case 4. Time 3 hr. 15 min .

Samples take n at thirty-minute intervals. Av. Fall Convulsions Sugar Cone. 8.5 mg. per hr. 2 a t 100 mg. %

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Fig. 5.-Case 5. Samples taken a t five-minute interva ls. After initia l drop eurve Is smooth with no abrupt changes until glucose infusion was int·errupted for a few moments and until peak was reached. DISCUSSION

In the analysis of our material we find that due to the rapid administration of dextrose most of our time was spent in the study of blood sugar values during their declining periods. It is, therefore, probable that irrespective of the effect of increasing and decreasing blood sugar levels on the incidence of convulsions, the mathematical possibility of convulsions occurring during the declining periods of our graphs is greatly increased over the possibility of their occurrence during increasing glycemic levels.

408

AMERICAN JOURNAL OF OBSTE'l'RICS AXD GYXECOLOGY GLYCEMIC LEVEL ON ADMISSIO:'\

TABLE I.

NORMAL

HYPO

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HYPER

I

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121 116 ----:;--1···----·-·--·-l----- --,2'""---l--··---2--- - - Av:-111.2 If'olin-Wu Normal-90-120 -- ·············································- --·---- ·-·-----96

69 64

2

I

II.

273 148 3

72 78 4

Somogyi-Folin TABLE

395

93

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AVERAGE RATE Ol!' FALJ, IN BLOOD SUGAR CONCENTRATI0;-;1 X::
SUGAR CONC. MG. o/o

Group I. Receiving no insulin. 21.5 222.0 124.0 8.5

Case 2 Case 3 Case 4

1 1

112

2

100

1 1 1

170 110

1 1 1

120

1 1

148

1

1

1

470 330 265

2

202

1 1

700 690

1 1 1 1 1 1 1 1 1 1

93 93 382 340 96 90 65 580 678 636

250

Group II. Receiving insulin 225.0

Case 6

50.0 40.0 188.0 40.0

Case 7

0.0

Case 8

Rise Case 9

93 34

57

26.0

Rise

Case 12

6.0 384.0 313.0 64.0 64.0

200.0

1Use

Case 14

140.0 0.0 20.0

204.0

Case 10 Case 11

Case 13

39.0 1098.0

250

9.0 810.0

188.0

188.0

Rise Rise JM,se

Rise Rise

29.0 52.0 137.0

112.0 0.0

24.0 15.5 314.0 64.0 46.0

MAYS-MC C'ORD:

BLOOD St:GAR lJEHcJ.,..; J;>; E I ' I. AM PHIA

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In that the occurrence of convulsions has been suggested to be due to a relative hypoglycemia, that is, a rapid fall in blood sugar level from a preexis6ng high er level to a lov.·er level, r egardless of the

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Period 1

2

Fig. 6.-case 6. Samples talten at thirty-minute lnt rvals. Convulsions Sugar Cone. Av. Fall Time 1 225.0 mg. per hr. at 170 mg.% 33 min. 1 50.0 mg. per hr. at 110 mg.% 1 hr. (Medication-Morphine and sod ium amytal) I. '

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Flg. 7.-cas Time 35 min. 30 min. 30 min.

7.

Samples taken a t Av. Fall 40.0 mg. per 188.0 mg. per 40.0 mg. per

thirty-minute Intervals. Sugar Cone. onvulslons at 250 mg. % 1 hr. hr. a t 120 mg. % 1 hr.

410

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY

absolute level, we have first selected a series of four cases which exhibited convulsive manifestations of eclampsia immediately preceding the study in whieh we gave rapid infusion of large doses of dextrose. In Case~ 1 and 3 it may be seen that no convubions occuned during the decline in blood sugar concentration. Case 1 is especially convincing because of the rapid

5

Fig. 8.-Cas Time 50 min. 1 hr. 30 min. 30 min. 3 hr. 30. min.

Period 1

2

Samples tak n Av. Fall 0.0 mg. 39.0 mg. R'i!e ot 1098 140.0 mg.

at thirty-minute int rvals. Sugar Con. onvulsions 1 per hr. at 93 mg.% 1 p r hr. at 34 mg.% per hr. per hr.

liiD

100

1M$

Period 1

2

Fig. 9.-<::ase 9. Time 35 min. 48 min.

+

5.

Sampl s taken at thh·ty-mlnute Intervals. Sugar Cone. onvulslons Av. Fall at 148 mg. % 1 0 mg. p r hr. at 57 mg. % 1 20 mg. per hr. (So<'llum amytal)

~1A YS·MC CORD:

.fll

BLOOD SUGAR LE\'ELfi I:\ E CLAMPSIA

decline in blood sugar value to a relatively subnormal value. In Case 2 the incidener· of convulsions was not increased in proportion to the rapidity of deeline in blood sugar levels. I n Case 3 although there was a slower rate of decline in blood sugar. the incidence of convulsions was greater than in Case 2. A study of the remaining charts shows, as summarized :i n Table II, that t lll'n· i~ no relationship between the incidence of convulsions anrl the rapid ity in. whiel1 l'Pla·

510

.

1111 I

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Pe riod l

Fi g. 10.-C"aR • 10. Time 1 hr. 50 min.

Samples t a k n a t

thirt~·- mlnute

Av. Fall 204 mg. per hr.

:

lnten •H i s.

C"onvulsions

Rugar Cone.

.

• z Fig. 11.-

Period l 2 3 4

5

1

a~c

Time l hr. 35 min. 1 hr. 30 min . 1 hr. 15 min . 32 min.

hr. 25 min.

+ 11.

Sampl s tak n a t Av. Fall 26 mg. per 6 mg. per Riae o( 384 mg. per 313 mg. per 64 mg. per

thirty-minute inte1·vnls C"onvulslons Sugar· Cone.

hr. hr. hr. hr. hr.

1 1 1

at 470 mg.% at 330 mg. % a t 265 mg.%

412

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY

tive hypoglycemic levels are sought as has been contended. Cases 6, 11, 13, and 14 showed no increased tendency, to develop convulsions, as the blood sugar was forced from its original level to absolute hypoglycemic levels as compared to the periods during which the blood sugar sought to return to its original level from an absolute hyperglycemia after glucose infusion. Case 8 on the other hand shows a convulsion during a declining period to an absolute hypoglycemia and yet shows no convulsions during a declining period from an absolute hyperglycemia of 580 mg. per cent. When compared with Case 11 we cannot see that this phenomena is of any significance in that the two charts show exactly opposite effects. In the analysis of cases in which the blood sugar was lowered by the use of insulin we find that fifteen convulsions occurred at normal or lower than normal values and seventeen occurred at definitely high values. Convulsions occurred irrespective of the blood sugar concentration ranging from 34 mg. per cent in Case 8 to 705 mg. per cent in Case 12.

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3

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Fig. 13.

Fig. 12.--case 12. Samples taken at thirty-minute Intervals. Av. Fall Convulsions Sugar Time 200 mg. per hr. 1 hr. at 202 9 mg. per hr. 40 min. Riae of 810 mg. per hr. 40 min. at 700 1 188 mg. per hr. 8 min . at 690 1 Fig. 13.--case 13. Samples taken at t n-mlnute Intervals. Sugar Av. Fall Convulsions Time at 93 JU&e of 29 mg. per hr. 1 31 min. at 98 62 mg. per hr. 1 30 min. Ri&e of 187 mg. per hr. at 382 48 min. 1 Riae of 112 mg. per hr. at 340 1 8 min.

Cone. mg. % mg.% Cone. mg.% mg. % mg. % mg.%

In view of the fact, as we have previously mentioned, that it is improbable that a convulsion should occur during the rise in blood sugar concentration during the early periods of glucose infusion, we finally present Cases 13 and 14, in which convulsions occur during periods of rapid increase in blood sugar concentration.

MAYS-MCCORD:

BLOOD SPGAR LEVELS 1~ J::CLAMPSIA

JJ;~

The irregular fluctuations in blood sugar in eclampsia, we think. have been indisputably presented. We are inclined, however, to agree with Stander and Harris 5 that many of these minor flunctuations might perhaps be attributed to error inherent in blood sugar determinations. This has been demonstrated by Seigle and Wiley 6 who show errors ranging from Ll per cent to over 20 per cent with variations of 0.5 mm. on the scale reading. We also observed during the collection of specimens that the patients were extremely restless and not infrequently had to be restrained. We believe this might at least produee a noticeable variation from time to time. We, therefore, have madP an observation of the variations in the blood sugar concentration of

Period 1 2

s

's 5

Fig. 14.-Case 14 . Time 38 min. 30 min. 1 hr. 17 min. 30 min. 30 min. 55 min.

Samples taken at thirty-minute lnte t·vals. Av. Fall Convulsions Sugar Cone. 0.0 mg. per hr. 1 a t 96 mg. % 24.0 mg. per hr. 1 a t 90 mg. % 15.5 mg. per hr. 1 at 66 mg. % Rille of 314 mg. per hr. 1 a t 680 mg. % Rille of 64 mg. per hr. 1 678 mg. % 46.0 mg. per hr. 1 (min. later) a t 636 mg.% (Sodium amytal)

a normal pr1m1para which data may be found in Table III. This patient in no way approached the emotional excitability and muscular activity of our eclamptic cases, and yet still showed a variation of 15 mg. per cent over the course of an hour. Although we do not feel that conclusions are justified from this siugle observation, we suggest that the fluctuations which have been observed in eclampsia may be due to muscular activity and might be observed in a normal patient under the same conditions of exeitement and activity.

4]4

AMERICAN JOURNAI, OF OBSTETRICS AND GYNECOLOGY TABLE

III.

BLOOD SAMPI,ES TAKEN AT FIVE-MINUTE l~TERVALS.

GLUCOSE

DETERMINED BY METHOD OF POLIN ON SOMOGYI FILTRATK NORMAL PRIMIPARAS AT MIDDLE OF FIRST STAGE

TIME

m•

LABOR

BI,OQD SUGAR CONCENTRATION

84 76

0 min. 5 10

79

74

15 20

7;)

74 74 78 69 75

25 30 35 40 45 50 55

74 78 CONCLUSIONS

1. Neither hypo- nor hyperglycemia is characteristic of eclampsia. The blood sugar concentration probably depends upon the patient's nutritional state and the degree of emotional stability and muscular activity immediately preceding the taking of the specimen. 2. The absolute blood sugar concentration has no effect whatsoever on the incidence of eonvulsions. 3. Convulsions oceur independently of the rate of decline in blood sugar concentrations. 4. Convulsions occur during a rapid rise in blood sugar concentration as well as during a rapid decline. REFERENCES

(1) Folin, 0., and Ma.ltmros, H.: J. Biol. Chem. 77: 421, 1928; 83: 115, 1929. (2) 11am. der Walle, N., 111M Noeriilin, E.: Geneeskund Tijdschr. Nederland. Indie. 73: 480, 1933. (3) Somogyi: J. BioL Chem. 70: 599, 1926; 86: 655, 1930. (4) Folitn, 0.: J. Bioi. Chem. 82: 83, 1929. (5) f}tander, H. J., and Ha.rri.son, E. P. H.: AM:. J. OBsT. & GYNEC. 18: 171 1929. (6) Siegel, I. A., and Wylie, H. B.: AM. J. 0BST. & GYNEC. 26: 29, 1933.

Vignes, H.: The Treatment of Hydra.mnios, Bull. Soc. d 'obst. et de gynec. page 45, 1933. Vignes treated a primipara who had hydramnion with calomel suppositories and intramuscular injections of iodized oil for almost twelve weeks until labor set in. By means of a graph he demonstrates the effect this medication had in stabilizing the height of the uterus. Labor was normal and a normal child weighing 3,800 gm. was delivered. The father of the child was found to have leueoplakia and unequal pupils. The placenta on histologic examination demonstrated changes almost eer· tainly indicative of syphilis. J. P. GREENHILL.