INDUCTION OF ABORTION BY COMBINED INTRA-AMNIOTIC UREA AND PROSTAGLANDIN E2 OR PROSTAGLANDIN E2 ALONE

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INDUCTION OF ABORTION BY COMBINED INTRA-AMNIOTIC UREA AND PROSTAGLANDIN E2 OR PROSTAGLANDIN E2 ALONE IAN CRAFT Institute of Obstetrics and Gynœcology, Chelsea Hospital for Women, London SW3

intra-amniotic urea and prostaglandin E2 induced abortion more than effectively prostaglandin E2 alone. The mean injection/abortion interval (10½ hours) was significantly shorter and the process was more often complete. This combined technique has advantages over alternative methods since it requires only a single initiating procedure and reduces nursing involvement. Combined

Summary

Introduction

VARIOUS techniques are being used to induce midtrimester abortion. The intra-amniotic injection of hypertonic saline and of urea has become popular at the expense of hysterotomy, and simultaneous infusion of oxytocin reduces the injection/abortion interval. 1,22 However, even with this amendment, abortion may take longer than 24 hours. The effectiveness of prostaglandins in inducing abortion has been assessed after their administration by various routes. Interest in the intra-amniotic route followed a report by Karim and Sharma 3 that successful abortion occurred within 14 hours in ten subjects receiving an injection of either 2-5-5 mg. of prostaglandin E2 or 25 mg. of prostaglandin F2
supervision.

In an attempt to find an intra-amniotic technique which is invariably effective within 24 hours of a single initiating procedure without the need of nursing supervision of an intravenous oxytocin infusion, I have compared the effect of injecting prostaglandin E2 alone with injecting combined prostaglandin E2 and urea. Methods The

patients

were

admitted for termination of preg-

nancy under the Abortion Act, 1967. The duration of pregnancy was 15 weeks or longer in each case and was

confirmed by ultrasound placental localisation.

investigation

at

the

same

time

as

Intra-amniotic Prostaglandin E2 A standard technique was used in all cases. The patient was instructed to empty her bladder, and 10 mg. of diazepam was given intravenously for premedication. Local anxsthetic (1% lignocaine) was infiltrated through the shaven abdominal wall at the site selected for puncture, and, using an aseptic technique, a Bard International angiocath (no. 1967) was passed into the amniotic cavity and the needle stilette withdrawn. The patency of the remaining cannula was then confirmed by noting the free flow of liquor into an attached syringe via a disposable three-way tap both initially and throughout the injection procedure. Liquor was not drained off before injection of 10 mg. of prostaglandin E2 in alcohol. Antibiotics were not instilled into the amniotic cavity, but a 5-day prophylactic course of oral trimethoprim and sulphamethoxazole tablets was given. The cannula was withdrawn and firm pressure was exerted over the site of puncture for 5 minutes before the patient was transferred back to the ward.

Intra-amniotic Prostaglandin E2 and Urea The technique used was essentially that described for prostaglandin E2 alone. After amniocentesis variable amounts of liquor were aspirated before injection of the urea solution. This was prepared by adding 80 ml. of sterile normal saline to a bottle of ’Ureaphil’ (Abbott Laboratories) containing 80 g. urea. The contents were dissolved by shaking and this procedure was facilitated by standing the bottle in warm water for a few minutes. The resulting volume of approximately 140 ml. was injected into the amniotic cavity irrespective of the amount of liquor withdrawn. This was followed by the injection of 10 mg. of prostaglandin E2 as described above. Assessment The progress of abortion

was

TABLE I-DETAILS OF INDUCTION OF ABORTION BY INTRA-AMNIOTIC PROSTAGLANDIN

Injection/abortion interval: Mean :l:S.B.M. 26 hours 49 minutes :1:4’45. * Additional injection of prostaglandin E. required to effect abortion. =

assessed

E2

by noting

the

1345 TABLE II-DETAILS OF INDUCTION OF ABORTION BY INTRA-AMNIOTIC PROSTAGLANDIN

Injection/abortion interval: Mean±s.B.M.=10 hours

of cervical dilatation by routine 4-hourly vaginal examinations. Analgesics were given liberally when indicated. A careful record was made of the exact time of abortion, whether the process was complete or not, and of the frequency of side-effects, especially vomiting and diarrhoea. After abortion, a speculum examination was made to exclude traumatic cervical injury, which has been reported after induced abortion.6 If, after 24 hours, abortion had not occurred, the procedure was repeated. Rhesus-negative patients were given anti-D immunoglobulin to prevent sensitisation. extent

Results

Abortion occurred in all fifteen patients who were given prostaglandins alone (table I) in a mean time of 26 hours 49 minutes (range 7 hours 40 minutes to 81 hours 5 minutes). However, six patients required an additional injection of 10 mg. of prostaglandin Eo at 24 hours and case 6 required two further additional injections of 20 mg. of prostaglandin Ez at 24-hour intervals.

In

case

15

an

additional intra-amniotic

possible at 24 hours because the sac of membranes was protruding through a partly dilated cervix into the vagina, but abortion rapidly followed the start of an intravenous oxytocin infusion. The products of conception were expelled completely in only four out of fifteen patients. There was no diarrhoea, but three patients vomited. Abortion resulted within 24 hours (mean 10 hours 30 minutes, range 3 hours 45 minutes to 23 hours 37 minutes) in all fifteen patients who were given prostaglandin Eo and urea (table 11). In case 18 (the patient who took the longest to abort), products of conception were found on routine vaginal examination in the morning, after the patient had slept through the night. The injection/abortion interval after the combined injection was significantly shorter than after prostaThe products glandin alone (t=3-20, p<0-01). were expelled completely in nine of the fifteen patients, but this frequency is not statistically greater than with Gastroprostaglandins alone (=3-39, P<0-1). injection

was not

intestinal side-effects

were more common with the combined method, three patients having one episode of diarrhoea each, occurring within 2 hours of the

injection.

Vomiting

was

significantly more prostaglandin Ea

in the group who received

(=8-57, rG0-O1).

common

and

urea

Eo

AND UREA

30 minutes d:l’19.

In no patient in either group did blood-loss require parenteral iron or a blood-transfusion, and no cervical injury resulted. Discussion

The results of using intra-amniotic urea and prostaglandins are particularly impressive, since, although the mean gestation times of the two groups were similar, a greater proportion of the group receiving the combined injection were primigravid subjects-i.e., 80% compared with 53%. The mean injection/abortion interval of 10 hours in the group receiving the combined injection is markedly less than that reported for alternative intraamniotic methods-e.g., 59 hours for urea alone, 40 hours for hypertonic salineand 184 hours for urea combined with oxytocin.22 It is also less than that reported in the various studies undertaken using prostaglandins given either intra-amniotically 4,8or extramembraneously,9-11 with or without the addition of intravenous oxytocin. The short time required to induce abortion with the prostaglandin/urea injection was associated with a progressive decline in plasma 6

oestrogens and progesterone, which sometimes started within an hour of injection. Details of this finding will be presented elsewhere. 12 The combined method has the advantage that, after a single simple initiating procedure, abortion will result within 24 hours even in primigravid subjects without the need to repeat therapy or infuse intravenous oxytocin. This ensures that nursing involvement is kept to a minimum and supervision of equipment required for the intrauterine injection of prostaglandins when given alone, especially by the extramembraneous The greater likelihood of route, is unnecessary. complete abortion is also important, since it reduces the inpatient stay. Slight disadvantages include the discomfort from uterine activity, which seems to be greater than that after intra-amniotic urea alone, and greater frequency of side-effects, especially vomiting. Vomiting may be related to alterations in the dynamics of absorption of prostaglandins into the systemic circulation from the amniotic sac due to the simultaneous administration of urea. Despite these minor problems, the overall benefits of

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the combined method have resulted in its routine use for dealing with mid-trimester termination in my department. A lower dose of prostaglandins than that given in the present study may be effective and could reduce side-effects; however, the injection/abortion interval might be increased. I thank the consultant gynxcological staff for permission to study their patients and the nursing staff for their assistance. The Upjohn Company and the Simon Population Trust supported this study.

against immunoglobulins of six different species showed strong (false) positivity in the ausria R.I.A. test. Thus antibodies to ingested globulins (e.g., of porcine, ruminant, or avian origin) cross-react sufficiently with the guineapig immunoglobulins used in this test to produce non-specific results. However, it should be emphasised that the ausria technique detected 2-3 times as many HBAg carriers among blood-donors as did routine counterelectrophoresis. Introduction

REFERENCES

DETECTION of the

Schulman, J. D., Lauersen, N. H. Lancet, 1971, ii, 606. Craft, I., Musa, B. ibid. p. 1058. Karim, S. M. M., Sharma, S. D. ibid. p. 47. Craft, I. J. Obstet. Gynœc. Br. Commonw. 1973, 80, 46. Bradley-Watson, P. J., Beard, R. J., Craft, I. L. ibid. p. 284. Greenhalf, J. O., Diggory, P. L. C. Br. med. J. 1971, i, 28. Gillmer, M. D. G., Friend, J. R., Beard, R. W. ibid. p. 434. Roberts, G., Gomersall, R., Adams, M., Turnbull, A. C. ibid. 1972, iv, 12. 9. Embrey, M. P., Hillier, K., Mahendran, P. ibid. 1972, iii, 146. 10. Miller, A. W. F., Calder, A. A., MacNaughton, M. C. Lancet, 1972, ii, 5. 11. Midwinter, A., Bowen, M., Shepherd, A. J. Obstet. Gynœc. Br. Commonw. 1972, 79, 807. 12. Craft, I. Unpublished. 1. 2. 3. 4. 5. 6. 7. 8.

SPECIFICITY OF THE DIRECT SOLID-PHASE RADIOIMMUNOASSAY FOR DETECTION OF HEPATITIS-B ANTIGEN ALFRED M. PRINCE D. JASS

B. BROTMAN H. IKRAM

Laboratory of Virology, New York Blood Center, and

Department of Pathology, Hospital-Cornell Medical Center, New York, U.S.A.

New York

The ’Ausria’ (Abbott Laboratories) direct solid-phase radioimmunoassay ten times as many positive reactions test detected (R.I.A.) did as counterelectrophoresis in 5089 volunteer donor bloods screened by both methods. The specificity of these reactions was investigated by preincubating sera with either hepatitis-B antibody (HBAb), normal guineapig serum, or normal human serum, to attempt neutralisation. In 21% of 81 sera which had been negative on counterelectrophoresis was the R.I.A.

Sum ary

positivity specific for the hepatitis-B antigen (HBAg), as indicated by clearcut neutralisation by HBAb. However, in 42% of these sera the R.I.A. positivity was found probably to be due to cross-reacting antiguineapig globulin antibodies, since the reaction was neutralised by normal guineapig serum. The R.I.A. positivity of remaining sera could not be clearly neutralised by HBAb or by guineapig serum, and hence was probably also not HBAg specific. These results were supported by post-transfusion follow-up studies: transfusion of HBAg-specific R.I.A.-positive blood resulted in serological evidence of hepatitis-B infection in 13 of 15 recipients, whereas transfusion of non-HBAg-specific R.I.A.-positive blood resulted in infection in only 1 of 18 recipients (P<0·001). Antisera

hepatitis-B antigen (HBAg) can of the carriers of hepatitis-B proportion identify virus. 1,2 Thus screening for HBAg in the serum of a

blood-donors is an essential component of measures to reduce the incidence of post-transfusion hepatitis.3 Unfortunately, the use of most current techniques for HBAg detection has resulted in elimination of only a small fraction of cases of post-transfusion hepatitis 4,5: most workers estimate that only 20-30% of blood which can give rise to post-transfusion hepatitis is being detected. A variety of radioimmunoassay (R.I.A.) procedures for detecting HBAg have been reported.6-11 These assays seem to be approximately 1000 times more sensitive than agar-gel diffusion in terms of the quantity of HBAg found; and they seem to identify 8-10 times as many HBAg carriers among blood-donors.10, 12,13 It has been suggested that these assays are highly specific. R.I.A. techniques are of two types-competitiontype assays in which HBAg is detected by its ability to compete with radiolabelled purified HBAg for reaction with antibody (HBAb), and direct solid-phase R.I.A.S in which HBAg is detected by its ability to bind radiolabelled purified HBAb to HBAb attached to a Although highly sensitive, solid-phase support. methods based on radiolabelled HBAg have the disadvantage that incubation-times of one to six days Such a delay are required for optimal sensitivity. would interfere seriously with efficient blood-banking procedures and would not permit the testing of labile blood products such as platelets and leucocytes. The direct solid-phase R.I.A. technique is sufficiently rapid and simple for routine blood-bank use. Indeed in the United States a commercial version of this method (’Ausria’, Abbott Laboratories) has been licensed. Blood-banks have been encouraged to gain familiarity with the use of this test and to institute this or an equally sensitive licensed screening method as soon as possible. There are no other licensed methods which approach the sensitivity of the direct solidphase R.I.A. It thus became important to examine the specificity of this test. The results of such an investigation are reported here. Materials and Methods

Solid-phase R.I.A. The solid-phase R.I.A. was carried out exactly as specified by the manufacturers, using guineapig HBAb-coated plastic tubes and 125I-labelled immunochemically purified guineapig HBAb supplied by Abbott Laboratories. In the first incubation phase of this test 100 jjd. of test serum incubated in the HBAb-coated tube for 18 hours at temperature. The tubes were washed seven times with 2 ml. of 0-OlAf " tris " buffer pH 7-2. This operation

was

room