Convulsive toxemia

Convulsive toxemia A report of 168 cases managed conservatively

GUY M. HARBERT, JR., M.D. HER BE R T A. C L A I B 0 R N E, JR., M . D . • HARRY S. McGAUGHEY, JR., M.D.t L EST ERA. W I L SON, J 11.., M. D . W. NORMAN THORNTON, JR., M.D. Charlot/twille, Virginia Existence 0/ eclampsia 0/ pregnancy as the cause of over 6 per cent of mal,ma. deaths indicates a continuing need for correlative revieu:s of Ireatment. During the 25 year period ending Dec. 31, 1963,168 patients with a diagnosis 0/ convulsive toxemia were treated at this institution. Delivery within an arbitrar)' lime limil after control of cont'ulsions or coma is nol considered an essential part of therapy. Treatment has bun continued as long OJ there is improvement in symptomatology, and termination of pregnancy has been considered primarily in Ihose patients Jhowing deterioration or abunce 0/ improl'emellt on medical management. This policy has resulted in an BI.S per cent incidence of spontaneous labor, an uncorrected fetal mortality of 21.6 per cent, and a maternal mortality of 4.7 per cent.

and eclampsia are arbitrary clinical divisions of a vasospastic disease peculiar to pregnant women. Although the incidence of severe disease is decreasing, the toxemias of pregnancy continue to be significant factors in maternal and infant mortality statistics. In 1963, 17.3 per cent of maternal deaths recorded by the National Center for Medical Statistics were related directly to the presence of this toxic state.? In addition, Eastman and Hellman l estimate that at least 30,000 stillborn and neonatal deaths result each year from toxemic pregnancies. An obvious continuing need for improved survival of both mothers and infants at risk from toxemia of pregnancy prompted review of results obtained at the University of Vir-

ginia Hospital in the management of this clinical entity. The present report relates to our experience in the management of 168 consecutive patients admitted to this institution with a diagnosis of convulsive toxemia.

PRE - EeL AMP S I A

Material

Diagnosis of eclampsia was made on the basis of hypertension, edema, and/or albuminuria associated with convulsions according to the classification proposed by the American Conunittee on Maternal Welfare. Other convulsive disorders were excluded. Between Jan. 1, 1939, and Dec. 31, 1963, 168 patients with the diagnosis of convulsive toxemia were managed. One hundred and sixty-one of these patients were delivered of 164 infants at the University of Virginia Hospital. Five patients were admittelil post partum and 2 patients died undelivered. The patients' ages ranged from 13 to 43 years with a mean age of 21.9 years. Fortynine per cent of the patients were 19 years of age or less and 75 per cent were under

From the Department of Obstetrics and Gynecology, University of Virginia School of Medicine. ·Present address: Hill Davis Medical Building, 3500 Kensington Avenue, Richmond, Virginia. tDied Feb. 25, 1967.

336

Volume 100 Number 3

Convulsive toxemia

25 years of age. The average number of pregnancies per patient was 1.2. However, 70 per cent of the gravidas were pregnant for the first time. Although the Negro population in the University referral area approximates 25 per cent, the incidence of eclampsia was essentially equally divided between the races, 51.2 per cent Negro and 48.8 per cent Caucasian. These figures affinn the documented susceptibility of the young primigravida and the Negro to this complication of pregnancy. Sixteen women, 31.4 per cent of the multigravid patients in the study population, gave a history of having had toxemia of pregnancy with an earlier gestation. Five of this group had a previous diagnosis of eclampsia recorded at the University of Virginia Hospital. Two multigravidas were diagnosed as having convulsive toxemia twice during the study interval. For purposes of this survey, prenatal care was defined as a patient being seen by a physician on at least one occasion prior to the onset of convulsions. Even by this liberal definition, 100 patients or 59.5 per cent of the convulsive series received no prenatal

Table I. Declining incidence of eclampsia Year

ITotal birth

1939-43 1944-48 1949-53 1954-58 1959-63

4.561 6,993 8,043 9,579 10,223

56 50 35 17 10

1.22 0.71 0.43 0.17 0.09

Total

39,399

168

0.42

Incidence

care. Other factors, such as hypertensive car· diovascular disease, renal disease, twins, diabetes, and polyhydramnios, generally con· sidered to predispose a gravid woman to the pathophysiology of toxemia, were known to exist in 19 patients prior to their convulsive episode. During the 25 year interval covered by this report, there were 39,399 consecutive pre· mature and term deliveries at this institution. Thus, the incidence of eclampsia for the entire series was 1 eclamptic pregnancy for every 234 infants delivered. In Table I, the rdative as well as the absolute frequency of eclampsia is shown to have declined from I in 81 births during the first 5 year interval of the review to 1 in 1,032 deliveries during the 1959 to 1963 period. Labor and delivery

Table II summarizes the method of initiation of labor and route of delivery. Onset of labor was spontaneous in 81.5 per cent of the cases. Forty-seven of the 83 patients in whom eclampsia antedated spontaneous initiation of labor were delivered within 48 hours of the first convulsive episode. In the other 36 patients, experiencing antepartum convulsions, the time interval between occurrence of convulsion and spontaneous onset of labor ranged from 93 hours to 42 days, the latter being a case of intercurrent eclampsia in a patient who experienced 3 convulsive attacks at approximately 31 weeks' gestation. It was elected to terminate pregnancy in 29 patients. No pregnancies were interrupted because of uncontrolled convulsions,

Table II. Method of initiating labor and route of delivery Type

0/

delivery

Vaginal Spontaneous labor Induced labor

Antepartum ulampsia

83 (1.42 days)* 18 (4--16 days) *

Intrapartum eclampsia

Postpartum eclampsia

20

34 1

Total

137 (81.5%) 19 (11.3%) 156 (92.8%)

Cesarean section Died undelivered

7 (5·25 days) * 2 110 (65.5%)

2

0 21 (12 .5%)

-Time interval between dia"no,iI of eclamp.ia and delivery.

337

0 37 (22.0% )

10 ( 6.0%) 2 ( 1.2%) 168

338

F,bruary I, 1968

Harbert et al.

Am.

J.

Ob,1. &< Gynec.

Table III. Maternal mortality Obstetric history at time of d,alh

Pat ient

Age ( yeaTs)

Duration of ge station (weeb)

V . F.-

16

37

0-1-0-0

1/10/39

j.L.

32

39

S-I-I-S

4/ 7/39

S. K.-

22

40

1-0-0-1

6/ 30/39

D. H.

37

30

Vnknown

6/12/40

L.M.

27

36

6-1·0-7

7/ 7/41

H.H.

37

35

0-0-0-0

11/19/43

M . H .-

15

40

1-0-0-1

3/27/44

1. S."

39

Unknown

4-1-0-5

12/ 9/44

Dale

0/

death

"Negro.

Table IV. Incidence of residual hypertension among 158 surviving patients Patients with adequate follow-up

125 (79.2%)

Patients with subsequent diagnosis of hypertensive vascular disease Pre-existing hypertensive vascular disease No previous history

3 24

Patients with subsequent normal blood pressure (follow-up from 6 weeks to 24 years) Patients with inadequate follow-up Pre-existing hypertensive vascular disease (no follow-up) Hypertension 6 weeks post partum (no follow-up) Hypertension on discharge (no follow-up) Normotensive on discharge (no follow-up)

seizures being brought under control in every instance prior to termination of pregnancy. In the majority of instances, artificial interruption of pregnancy was performed because of unsatisfactory control of the morbid state by medical management. Occasionally, the procedure was performed at the discretion of the attending physician. Ten eclamptic women were delivered by cesarean section. While the over-all rate was

27 (16.9'/0)

98 (61.6%) 3 9

33 (20.8%)

5

16

6 per cent, only 6 cesarean sections were performed because of eclampsia per se. In 4instances, abdominal delivery was performed for other obstetric conditions: 1 an extraperitoneal procedure for cephalopelvic disproportion after 21 hou·rs of labor complicated by rupture of the amniochorionic membranes and intrapartum convulsions; 1 patient had a cesarean section for cephalopelvic disproportion and convulsed post partum;

Volun.e 100 Number 3

Convulsive toxemia

339

Temporal relationships Con vulsions to delivery or death 5 days

4 hours

I

Delivery /0 death

Autopsy obtained

Autopsy findings and/or cause of death

31 hours

Yes

I. Bilateral lobular pneumonia 2. Acute puerperal endometritis and sepsis 3. Uremia

6 hours

No

I. Cardiovascular collapse

Postpartum

70 days

Yes

I. 2. 3. 4.

39 hours

U ndeliVt'rl'd

Yes

1. Lobular pneumonia 2. Hemorrhagic nerrosis of liver 3. Pulmonary edema

26 hours

24 hours

No

1. Pulmonary edema

46 hours

Undelivered

Yes

1. Hemorrhage and necrosis of liver 2. Pulmonary edema 3. Hydrothorax

Bilateral lung abscesses Fibrinopurulent pleurisy Extensive healing necrosis of liver Osteomyelitis fourth and fifth ribs

4 hours

5 hours

Yes

1. Acute diffuse glomerular nephritis 2. Pulmonary edema

7 days

4 days

Yes

1. Confluent lobular pneumonia 2. Empyema of right chest

and 2 deliveries were repeat cesarean sections. Maternal mortality and morbidity

A maternal mortality of 4.7 per cent was experienced. During the first 6 years of the study interval, 8 deaths occurred. The circumstances relating to the maternal deaths are tabulated in Table III. Between Dec. 9, 1944, and termination of the study period on Dec. 31, 1963, 108 consecutive eclamptic patients were managed without loss of a mother. Follow-up ranging from 6 weeks to 24 years, on 125 of the 158 surviving patients is given in Table IV. Ninety-eight of the surviving patients had a normal blood pressure when last examined 6 weeks or more following delivery. Twenty-seven patients were found to have cardiovascular disease at an interval of 6 months or longer following termination of their eclamptic pregnancy. Eighteen of these 27 patients had a lengthy interval, more than 5 years, of normal blood pressure recordings, subsequent to

their dia!,'l1osis of eclampsia and thereafter developed hypertension. Hypertension preexisting eclampsia was documented in three patients. Follow-up on 33 patients was inadequate. Perinatal mortality

Interrelationships of perinatal mortality to birth weight, number of infants at risk, and time interval between occurrence of convulsions and termination of pregnancy are collated in Table V. Occurrence of 37 fetal deaths among the 171 infants at risk yielded an uncorrected perinatal mortality of 21.6 per cent. Twenty-two infants were stillborn and 13 infants died neonatally. Two infants were undelivered at the time of maternal death, one estimated at 30 weeks' and one at 35 weeks' gestation. Twenty of the 37 infants lost were premature, 4 infants weighing less than 1,000 grams. In 2 instances the estimated duration of pregnancy and birth weight of the fetus were unrecorded. Among the 13 term-sized infants lost, 7 were de-

340

Harbert et 01.

Am.

F.·b,uary t, 1968 Ob,!. & Gyote.

1.

Table V. Perinatal mortality Termination of preg'!!nc_y_____ I---E-l-ec-t-h-'e--- I Spontaneous I 1

Time ( convulsions to delivery) Less than 72 hours

Birth weight ( grams)

Greater than 72 hours

~~f~~f~ I Pt~~~;tal I ~~f~~i~-I-Pt~:;tall-I-a~-f-~~-·s~-s -I--p-e-~-~n-s;-ta-l-

< 2.500

Unknown

4

2 (50.0%)

29 36 1

< 2,500

10 12

4 (40.0%) 1 ( 8.3%)

20 19

> 2,500

> 2,500

6 (20.6~~) 8 (22.2%)

o

< 2,500

> 2,500

Unknown

3

4 29 2

0

70

16 (22.8%)

61

17 (28.0%)

38

2 ( 5.2%)

10 (50.0 r ; ) 2 (10.5':'; )

Unknown Post partum

Total

0 2 ( 6.8'::: ) 0

Undelivered at time of maternal death

2 Total

29

7 (24.0';{ )

livered within 24 hours of the onset of convulsions and 3 were stillborn between 24 and 48 hours. Only 3 term stillborn infants remained in utero for more than 48 hours after onset of convulsions, delivery occurring on the third, fourth, and fifth hospital days. A 28 per cent perinatal mortality resulted from 3 neonatal deaths and 14 stillbirths in the 60 patients (61 infants) delivered 72 hours or longer after admission. Birth of infants weighing 1,185, 1,750, and 1,070 grams on the fourth, eighth, and sixteenth hospital days, respectively, accounted for the neonatal deaths in this group. In 4 of the 14recorded stillbirths, fetal viability was not in evidence on initial examination of the mother. All stillborn infants delivered 6 days or longer after onset of convulsions weighed less than 2,000 grams. There were 6 stillbirths, 32.1 per cent perinatal loss, among the 19 patients in whom labor was induced. Among the 137 women in whom labor ensued spontaneously there were 140 infants at risk with 28 fetal deaths, a perinatal m(,)rtality of 20 per cent. Ten instances of cesarean section carried a 10 per cent perinatal loss. In the 6 instances in

140

~!l

(20.W;)

171

2 37 (21.6% )

which t'c1alllpsia was the indication for ct'sarean section, all infants survived. Comment

The University of Virginia Hospital, 10catt'd in the Piedmont section of Virginia, srrves as a maternity referral center for 9 surrounding counties as well as more distant parts of the Commonwealth. Since 1940 it has consistently recorded between 1.85 and 2.11 per cent of the yearly births in the state. 6 An over-all incidence of 1 case of eclamptic toxemia for every 234 births is well above the 1 in every 500 to 800 deliveries estimatt'd for the United States in generaP and probably reflects the referral nature of the patient population rather than the true incidence of this complication within the geographic confines of Virginia. The declining incidence of eclampsia in this hospital (Table I) could refiect, in part, a change in patient referral patterns but may also be attributed to more universal acceptance of prenatal care and earlier recognition and hospital treaunent for pre-eclampsia. At the University of Virginia Hospital, sudden weight gain without proteinuria or

Volume 100 Number 3

hypertpnsion is the only manifpstation of the toxemic syndrome managed out~ide the hospital on either the ward or private service. Once the patient develops signs and symptoms of toxemia, treatment becomes an effort to institute measun"s to bring about reversible changes in deranged physiology. Such an undertaking must attpmpt to prevent convulsions, decrease elevated blood pressure, reduce arteriolar spasm, and correct abnormal electrolyte and fluid distributions. Once the patient is admitted to the hospital, therapy is based primarily upon usc of sedation and bed rest. Paraldehyde, frequently used in the earlier period of this review, has not been employed in recent years. Sodium amy tal has been used on occasion to control the initial convulsive state. Morphine sulfate and phenobarbital have remained the mainstay of therapy throughout the senes. Magnesium sulfate has been consistently employed for prevention and control of eClamptic convulsions. In adequate amounts it is reliable and safe, the most frequent error in magnesium therapy being inadequate dosage. Since 1954, the magnesium ion has been administered exclusively by the intravenous route. It is felt that this technique is superior to intramuscular injection in that this mode of administration permits a more rapid achievement of therapeutic blood levels and allows more meticulous control of dosage. Maximum therapeutic effect, gauged by laboratory studies and clinical observations, has been best obtained by maintenance of serum magnesium levels approximating 6 to 8 mEq. per liter,s. 5 a concentration well below the level of toxicity.2 As much as 40 to 60 Gm. of magnesium sulfate has been administered in a 24 hour period without untoward symptomatology. Documentation of a profound inhibitory action of the magnesium ion upon uterine activity and of a general slowing of the progress of labor incident to the use of this central depressant does not detract, in our opinion, from its use as the anticonvulsive agent of choice in severe toxemia of pregnancy but should call attention to one of the

Convulsive toxemia

341

side effects of the drug- that may necessitate institution of concomitant resources. 4 In the eclamptic patient, fluid replacement has been based on measured and insensible loss without emphasis on either fluid restriction or hydration. Diuretics, oxygen, and digitalis have been employed when specifically indicated. Constant emphasis has been placed upon meticulolls individualization of therapy and dosage in each case, care being exerted to avoid excessive medication, which can be as potentially hazardous to mother and fetus as undertreatment of the disease. Antihypertensive drugs have been employed only infrequently despite their unquestioned ability to reduce blood pressure and relieve peripheral vasospasm. In our experience, use of these drugs has not appeared to offer any unique advantages over other methods of treatment and their employment may be accompanied by the potential hazard of a precipitous fall in blood pressure. Although it is generally recognized that termination of pregnancy is the only definitive cure for eclampsia, the policy at the University of Virginia Hospital in regard to timing of delivery has been consistently conservative. It is considered unwise to superimpose the additional trauma of labor, delivery, or operation upon the patient in a recently convulsive or comatose state. Termination of pregnancy in the treatment of eclampsia has been reserved primarily for those patients showing deterioration in the course of the disease or absence of improvement on adequate medical therapy. It is the belief of the Department of Obstetrics that it is impossible to fully evaluate the patient within 24 or 48 hours after treatment has been initiated. Convulsions are usual\y control\ed within the hour, but other indications of substantial improvement may not be witnessed prior to the fourth or fifth day of therapy. Treatment has been continued as long as there is improvement in symptomatology. While there is no objection, in principle, to elective induction near term subsequent to adequate treatment, it has been employed only rarely, the greater majority of pregnancies having terminated in spontaneous onset of labor. Elective induc-

342

Harbert et 01.

tion of labor following satisfactory response to therapy may be contraindicated prior to near term gestation in the interest of greater fetal maturity. A philosophy of conservatism in regard to termination of pregnancy complicated by eclampsia might render speculation as to whether the 21.6 per cent fetal mortality rate could not have been decreased further by more frequent and more prompt temlination of pregnancy. However, it is conceivable that any potential advantage inherent in early induction would be offset by a greater incidence of prematurity. It seems unlikely that a policy of earlier delivery would have diminished the mortality among the 20 already premature infants that did not survive. In like manner, it is doubtful that earlier delivery would have altered maternal mor-

Am.

F.hruary 1. 1968 & Gynec.

J, Obsl.

tality. In only the first and eighth cases of the maternal Illortality n·\'iew did the fetus rpmain in utero for longer than +8 hours following admission. The other patipnts either died within +8 hours of admission or experiellcl'd onset of cOllvulsions during the intrapartulIl or postpartum periods. Advprse effects on ultimate maternal prognosis occurrt'd in 24 patients known to have den'lop<'d persistent hYp<'rtension after inter\'als varying from 6 months to more than 5 years of normal blood pressure recordings subsequent to termination of their eclamptic pregnancy. However, loss to follow-up of 20.8 per cent of 158 survi\'ing patients negates valid interpretation of the relationship of prolongation of pregnancy complicated by eclampsia to the incidence of residual hypertension in this survey.

REFERENCES

1. Eastman, N. J., and Hellman, L. M .: Williams Obstetrics, ed. 13, New York, 1966, AppletonCentury-Crofts, Inc. 2. Goodman, L. S., and Gilman. A. : The Phannaeologieal Basis of Therapeutics, ed . 3, New York, 1965, The Macmillan Company. 3. Hall, D. G.: Obst. & Gynec. 9: 158, 1957. 4. Hall, D. G., McGaughey, H. S., Jr., Corey, E. L., and Thornton. W. N., Jr.: AM . J. OBST. & GVNEC . 78: 27, 1959.

5. Pritchard, 131, 1955,

J.

A.: Surg., Gynec. & Obst. 100:

6. Statistical Annual Report of the Virginia State Departm .. nt of Health; Richmond, 1962, Commonwealth of Virginia . 7. Mortality, in Vital Statistics of the United States, Washington, D. C .. 1963, United States Government Printing Office, vol. II, Part A.