Effects of intra-amniotic injection of hypertonic saline on uterine activity, blood and amniotic fluid volumes, and electrolyte concentrations

Effects of intra-amniotic injection of hypertonic saline on uterine activity, blood and amniotic fluid volumes, and electrolyte concentrations

Effects of intra-amniotic injection of hypertonic saline on uterine activity, blood and amniotic fluid volumes, and electrolyte concentrations LARRY...

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Effects of intra-amniotic

injection of hypertonic

saline on uterine activity, blood and amniotic fluid volumes, and electrolyte concentrations LARRY

L.

WAYNE

L.

CHARLES Seattle,

BREWER,

M.D.

JOHNSON, A.

HUNTER,

M.D. M.D.

Washington

Intraouular injection of hypertonic saline successfully initiated labor in 16 patients. There was a net increase in amniotic fluid volume associated with a decreased blood volume within 2 to 4 hours following injection. The sodium chloride in the amniotic sac is diluted by the influx of water and is lost into the maternal circulation where increased serum sodium and chloride concentrations were observed. Amniotic fluid pressures were continuously monitored. Uterine activity increases shortly after injection and continues to increase until delivery is accomplished.

HYPERTONIC saline has proved to be an effective agent for the induction of labor for therapeutic abortion after 14 weeks or to expel the products of conception following fetal death.lm4 There are alterations in sodium and chloride concentration with attendant shifts in water following intra-amniotic injection of hypertonic saline. This is a report of the electrolyte and volume changes of serum and amniotic fluid in 16 patients. The results of continuous amniotic pressure recordings are also presented.

Materials

and

remained in place until delivery to inject solutions, withdraw samples, and monitor intrauterine pressure. Whenever proper placement of the catheter was in doubt, a small amount of radiopaque dye was injected and intra-amniotic position confirmed by x-ray. All control sampleswere drawn and base-line measurementswere made prior to injection of hypertonic saline. Dilution techniques were used for volume determinations. For blood volumes, 4 to 5 PC of radioiodinated serum albumin (RISA1131) was injected into the antecubital vein. After a 10 minute mixing period, a sample was drawn from the opposite arm. Volume was automatically computed on the Volemetron. Serial microhematocrits were drawn and technique standardized to increase the accuracy of the volume determination. Amniotic fluid volumes were determined by three methods: RTSA-I131, Congo red, and sodium aminohippurate (PAH) . RISA1131was not used for both blood and amniotic fluid volumes in the same patient. After the total counts had been determined, 1.5 to 4.0 PC of RISA-I131 was injected into the amniotic sac. Volume was calculated from

methods

Table I presents the clinical data of the patients studied. With sterile surgical technique, an amniocentesis was carried out with an 18 gauge thin-wall needle. Polyvinyl tubing with an outside diameter of 0.036 inch (0.9 mm.) was introduced through the needle and the needle removed. The catheter From the Department of Obstetrics Gynecology, Division of Reproductive Biology, University of Washington School of Medicine.

and

Supported in part by Grant No. HD-01366, National Institutes of Health, United States Public Health Service.

1078

Volume 101 Number

Sera

8

Table I. Clinical

data

and volumes

electrolyte

changes

after

hypertonic

saline

1079

on 16 patients

-___

Patient L. c. I. s. Y, E. 0. R. D. A.

_-.

Gravida 3 2 4 3 3

Age

ia 20 32 29 22

M. R. B. K. P. P. A. C. S.

G. W. H. M. P. D. D. B. J.

g.1

.

Weeks’ gestation 34 39

ia

28 39 19

1 4

NaCt injected (Gm.) 40 41 40 40

20 15 20 20 20 20 20 20 20 20

26 30 24 “1 31 30

: 5 3 1 4 4

28

31

40 30 40 40 40 40 40 40 40

21 ia

31

17 33

40

26

36

38

Per cent solution of NaCl 20 15 20 20 15

28

18

37 29

28 36

28

+ 5OOr

Control

I

2

3 Hours

4 after

5

6

7

8

9

injection

Fig. 1. Net increase or decrease in blood and amniotic fluid voIumes after intra-amniotic injection of hypertonic saline.

the counts per ml, in the samples. It has been shown that very little of this material is lost from the uterine cavity in 8 to 9 hours5 Further evidence of the reliability of this method was obtained in other patients not included in this series by injecting isotonic saline into the amniotic sac in 50 to 100 ml. increments over a period of 9 hours. The calculated volume was within 6 per cent of the estimated volume at all times. A modification of the techlnique described by Dieckmann and Davis6 was used for volumetric determination of amniotic fluid with Congo

IO

___~-

Fluid withdrawn

Latent fwriod

A&x labor

Indication

(ml.)

(hr.)

(hr.)

Fetal death Fetal death Fetal death Fetal death Therapeutic abortion Fetal death Fetal death Fetal death Fetal death Fetal death Fetal death Fetal death Fetal death Fetal death

20 20 0 20 20

6 3 4 19 35

6 4 2

30 200 20 20 100 “0 10 0 50

25

4 2

11 9 9

5 a 3

11

3

I 12

‘I 3

20a

177

Fetal

death

a ia

a 2

4,

-24 --

red. Seven to 10 ml. of 0.05 per cent solution was injected into the amniotic sac after control specimens were obtained. Samples of this fluid were centrifuged at 50,000 r.p.m. and the supernatant filtered through a NO. 52 Whatman filter. The optical density of the filtrate was then compared with the control samples at 500 mp with a spectrophotometer. The concentration of Congo red in amniotic fluid was determined from a standard dilution curve and the volume calculated. The PAH method used was that described by Charles and Jacoby.7 Two milliliters of 20 per cent PAH was injected into the amniotic sac. The PAH concentration was determined by a diazo reaction and spectrophotometric analysis at 540 mp. When PAH is used for amniotic fluid volume in normal pregnancy, there is a gradual loss of the material from the amniotic sac. Using normal controls, a disappearance curve was plotted for 10 hours following the injection of the PAH. Volume determinations in this study were then appropriateIy corrected. Sodium and chloride concentrations in serum and amniotic fluid were determined by standard analytical methods on an autoanalyzer. Osmotic pressures were calculated from the freezing point depression with a calibrated osmometer. Amniotic fluid pres-

1080

Brewer,

August

Johnson, and Hunter

15, 1968

Am. J. Obst. & Gynec.

Table II. Means and standard deviations of volumes and electrolytes Hours Study

No. of patients

Amniotic fluid volume (c.c.) Blood volume (cc.) Amniotic fluid Cl- (mEq./L.) Amniotic fluid Na+ (mEq./L.) Amniotic fluid osmotic pressure (mOsm./L.) Serum Cl- (mEq./L.) Serum Na+ (mEq./L.) Plasma osmotic pressure (mOsm./L.)

co”,+0

8 6 5 5

Control

6 7 7

2812 107 2 139 t

6 3 2

8

280 2

4

105’ CO”,,O, Hours

after

injection

2

I

1,114 r 441 5,817 + 560 111 ? 7 1462 7

2 352 + 628

1,505 5,360 589 617

2

58

2 56

1,2292 177

’ I

110 + 141 +

4 3

283 +

1

’ 2

after

’ 3 Hours

1,511 5,054 523 608

3 1,664 k 461

+ 422 + 655 k 61 + 53

489 + 18 582 -t 87

1,153 2 80 110 + 3 141 t 3 2872

’ ’ n 4 5 6 after injection

1,030 + 133 115+ 4 144+ 4 288 +

6

* 7

injection

’ 6

8 9

‘ IO

Fig. 2. Sodium and chloride concentrations and osmotic pressure in amniotic fluid after intraamniotic injection of hypertonic saline.

Fig. 3. Sodium and chloride concentrations osmotic pressure in serum after intra-amniotic jection of hypertonic saline.

sures were continuously monitored using an open-end polyvinyl catheter with a Statham P-23 strain gauge transducer and a Sanborn series350 carrier amplifier and recorder. The pressure signal was electronically integrated, reset at one-minute intervals, and recorded on a separate channel of the recorder as mean millimeters of mercury per minute.

terminated in delivery in all patients without supplemental oxytocic agents. The means and standard deviations of blood and amniotic fluid volumes and electrolyte concentrations are presented in Table II. Volume changes. The net changes in blood and amniotic volume are presented in Fig. 1. During the first 4 hours all blood volumes were below the control value. After 5 hours blood volumes were back to control levels. The initial lossis significant in 2 to 4 hours (p < 0.05). The significance of the

Results

of hypertonic saline into the amniotic sac successfully induced labor and Injection

and in-

7

Sera

electrolyte

and

volumes

changes

after

hypertonic

)f hypertonic saline

---_-~-

4 1,562 5,150 442 480

982 2 111 t 14oc 289

5

+ 519 2 335 2 29 !I 48

+

72 4 3 8

saline

1,548 410 430

6 + 498 f 2

17 24

1,306 5,805 368 393

7

+ 592 2 598 + 24 + 17

1,401 328 407

8

+ 383 + +

15 79

1,218 5,865 309 346

9 + 489 C 665 +_ 34 k 14

1,213

587

961 2 130 118+ 3 1465 7

871 + 101 114+ 4 143 + 5

952 * 165 1165 4 144 + 3

748 + 184 1152 3 1452 5

2912

294+

297

'945

4

4

difference between means was calculated using the t test. All amniotic fluid volumes increased within the first hour and remained above control values for the duration of the study. This increase becomes significant 2 to 3 hours after injection (p < 0.01) . Net changes in amniotic fluid were calculated after correcting for the volume introduced by injection of hypertonic saline and samples withdrawn. Electrolyte changes. Fig. 2 represents the mean values of sodium and chloride concentrations and osmotic pressure in the amniotic fluid. There is a graduaI decline from the initial peak following injection of the hypertonic saline. Mean serum electrolyte values are presented in Fig. 3. A rise in serum sodium, chloride, and total solute occurs over the first 6 to 8 hours, correlating with the clinical observation of patient thirst. The increase in plasma osmotic pressure is significant at 5 hours (p < 0.01). At 10 hours, the values were returning toward normal. Amniotic fluid pressure. The average duration of time from injection of hypertonic saline to delivery was 16 hours. The average length of active labor was 4 hours. In order to compare the amniotic fluid pressure recordings from patients with varying lengths of latent and active labor, each record was divided into five segments. With a clinical definition of labor (painful contractions plus cervical effacement or dilatation), the records were divided first into control, latent, and active phases. The latent and active phases were then arbitrarily halved, yielding

+

2

1081

. 10

---

C 470 280 322

" 45 -t 17

II:!? It3

1

+_ 41 1 6

2

five parts to each labor. This method is demonstrated in Fig. 4, with the amniotic fluid pressure graph of one patient (S. J.) . The points on this graph represent the mean level of (mm. Hg) amniotic fluid pressure for each hour. An arrow marks the onset of active labor. This graph also demonstrates the consistent findings of an increase in uterine activity within a short time following injection of hypertonic saline. The average pressure with standard deviation for each phase of labor is shown in Fig. 5. Significant increases (p < 0.01) were found between control values and latent phase as well as between latent and active phases of labor.

Comment There are rapid and definite shifts in water and electrolytes following intra-amniotic injection of hypertonic saline. Water quickly diffuses into the amniotic sac, causing an early increase in amniotic fluid volume and a decrease in circulating blood volume. King, Friedman, and Steer,8 with Naz4, demonstrated increased serum sodium followed by increased electrolyte excretion in the urine. By calculating the total quantity of saline present in the amniotic sac by multiplying volume by concentration, we find the total quantity of salt decreasing even though volume is increasing. In other words, salt is leaving the amniotic cavity as well as water coming in. This would account for the concomitant increase in serum electrolyte

1082

Brewer,

August 15, LAR Am. J. Obst. & Gynec.

Johnson, and Hunter

26 36

24- c 24

t

T

I

Late

4 4-

control Control

latent I--

latent phose

phase

2

4 Hours

,## 66 ofter

* 5 8 IO injection

12

:,o v$ I I L 14 I6

Fig. 4. Uterine activity graph of one patient (S. J.) to illustrate phases of labor. Mean millimeters of mercury pressure were obtained by electronic integration of the amniotic fluid pressure signal.

concentration

and decrease in plasma vol-

ume. The reason abortion follows injection of hypertonic saline is not understood. Hendricks, Helfand, and Caldeyro-Barciag have shown that hypertonic saline given intravenously will induce active labor in some patients. Hendricks and Tucker-lo have also demonstrated a lack of direct myometrial stimulation by hypertonic saline. Continuous and intermittent recordings of amniotic fluid pressure have been used to demonstrate an increase in uterine activity within a short time following saline injection.ll? I2 The uterine activity increases from the usual lowamplitude high-frequency contractions of pregnancy to a prelabor patternI and finally

REFERENCES

1. 2. 3.

4. 5.

6. 7.

Fig. 5. Comparison of mean uterine activity phases of labor for all 16 patients, illustrating gressive rise in uterine activity even through phase of hypertonic saline-induced labor.

into progressive clinical labor. This has the appearance of the changes that occur over the final 2 weeks of a normal pregnancy condensedinto a few hours. The procedure of intra-amniotic hypertonic saline injection in inducing labor was successful in all 16 patients studied. No seriousside effects or complications occurred. In view of the rapid changes observed, the useof intra-amniotic saline may be hazardous in patients with cardiovascular or renal disease.

8.

Jaffin, H.,

Kerenyi, T., and Wood, E. C.: AM. J. OBST. & GYNEC. 84: ,602, 1962. Ruttner, B.: Obst. & Gynec. 28: 601, 1966. Short, R. V., Wagner, G., Fuchs, A., and Fuchs, F.: AM. J. OBST. & GYNEC. 91: 132, 1965. Bora, E.: AM. .I. OBST. & GYNEC. 91: 1148, 1965. Nelsen, E. D., Hutchinson, D. L., Hallet, R. L., and Plentl, A. A.: Obst. & Gynec. 3: 598, 1954. Dieckmann, W. J., and Davis, M. E.: AM. J. OBST. & GYNEC. 25: 623. 1933. Charles, D., and Jacoby, H. E.: Ati. J. OBST. & GYNEC. 95: 266, 1966.

in the prolatent

9.

10. 11. 12. 13.

King, T. M., Friedman, J., and Steer, C. M.: Bull. Sloane Hosp. Women 10: 14, 1964. Hendricks, C. H., Helfand, T., and CaldeyroBarcia, R.: Aol. J. OBST. & GYNEC. 77: 387, 1959. Hendricks, C. H., and Tucker, G. J.: AM. J. OBST. & GYNEC. 78: 13, 1959. Turnbull, A. C., and Anderson, A. B. M.: J. Obst. & Gynaec. Brit. Comm. 72: 755, 1965. Wiqvist, N. E. and Eriksson, G.: AM. J. OBST. & GYNEC. 88: 75, 1964. Reynolds, S. R. M., Harris, J. S., and Kaiser, I. H.: Clinical Measurement of Uterine Forces in Pregnancy and Labor, Springfield, Illinois, 1954, Charles C Thomas, Publisher, Chap. 6, p. 124.