- Email: [email protected]
A new method of exchange transfusion in utero
A new method of exchange transfusion Cannulation
J.
of vessels
SEELEN,
H.
VAN
T.
ESKES,
on the fetal
placenta
M.D. KESSEL.
M.D.
M.D.
H.
VAN
LEUSDEN,
J.
BEEN,
M.D.
J.
EVERS,
I.
VAN
L.
PEETERS,
M.D.
W.
VAN
VELDEN,
F.
side of the human
in utero
M.D.
M.D. GENT, DER
M.D. M.D
ZONDERLAND
Nijmegen,
The
Netherlands
LILEY,’ in 1963, introduced the intrauterine intra-abdominal infusion of concentrated blood in cases of threatening intrauterine fetal death clue to erythroblastosis fetalis. An intrauterine exchange transfusion, however, would seem the treatment of choice in these cases. Freda and Adamsons’ succeeded in exchanging fetal blood through the femoral artery. A disadvantage of this method is the necessity of rupturing the membranes with increased risk of immature or premature labor. The present report gives a method for intrauterine exchange transfusion with intact amniotic sac. The idea for this method crossed our mind during intrauterine operations on pregnant monkeys,“-” performed according to the technique of Reynolds, Paul, and Huggett. l’) It appeared to be possible to reach th? vessels of the fetal side of the
From the University Department Obstetrics and Gynecology, St. Rndboud Hospital.
placenta and to cannulate these ves,sels with free flow, without any damage to the amniotic sac. Case
report
Mrs. v. A-D., a 29-year-old gravida 6, para 3, was a sensitized Rh-negative mother (A cde/ cde) and who was sent to us for the first time in the twenty-eighth week of her pregnancy. She had a bad obstetrical history; the only child alive has serious neurological damages. Pregnancy proceeded normally although she had to be admitted because of premature uterine contractions. With the saline and the indirect antiglobulin methods, titers of rhesus antibodies (anti-D) of l/l and 1,312, respectively, were observed. From rhesus genotyping of the former children it could be derived that the husband of our patient was homozygous for the D-antigen (B, CDe/cDe) The findings in the amniotic fluid indicated that the fetus was suffering from a severe form of hemolytic disease. lx, I* In the thirty-fourth week of pregnancy, we concluded that fetal death was impending. At that moment, we had to choose between induction of labor and an attempt at intrauterine exchange transfusion. The fact that her last
of
872
Volume Number
95 6
Exchange
prematurely born child (36 weeks) died of respiratory distress made us prefer the latter procedure. The placenta was localized with IsrI-albumin13 and was found to be situated in the right front part of the uterus. Median line laparotomy was performed under general anesthesia. Neither inspection nor palpation or transillumination with a strong fiber light source revealed the exact location of the placental margin. Guided by the radioisotopic placental localization, a 3 cm. incision was made in the myometrium high in the lower part of the uterus just left of the midline and carried down to the decidual layer (Fig. 1). Blunt dissection with two nontoothed forceps separated the decidua and chorion easily from the amnion. The margin of the placenta could be reached easily by the exploring finger between the amnion and the chorion at a distance of 2 to 3 cm. to the right of the incision. In further loosening the chorion from the amnion, again only using the finger, a totally unexpected complication took place. We arrived in the area of the former transabdominal amniotic puncture sites and, at several small spouts of fluid this moment, through these puncture holes occurred. Obviously, the closure of these holes is accomplished only by the chorion and,/or decidual tissue and not by healing of the amnion itself. Surgical closure of these holes seemed impossible. Ring-
Fig. 1. The bulging.
myometrium
has been
incised
transfusion
in utero
873
shaped forceps were placed upon the myometrium close to the placental edge, and the amniotic sac was further separated from the chorionic plate. By manipulating the forceps, the chorionic plate with its vessels was brought into view. A small vein near the margin was cannulated over a length of 10 to 12 cm. with an 8 inch polyvinyl catheter (i.d. 0.015) which was fixed in the vein by atraumatically suturing the vein to the chorionic plate (Fig. 2, a and b j. Blood was obtained easily. The results of thv immediately performed analysis are given in Table I. An exchange transfusion of 670 ml. of heparinized fresh A cde/cde blood was prrformed without any difficulty by removing and replacing 8 ml. of blood at a time during 110 minutes. Data relevant to this exchange transfusion are given in Fig. 3. The catheter was then removed and the vessel tied. The myomrtrium was closed in two layers. The uterus seemed to be contractile. An open-tip saline filled catheter was introduced through an amniotic puncture to record intrauterine pressure.l* Contractions of 15 mm. Hg with a frequency of 2.0 contractions per 10 minutes were observed. Both mother and fetus tolerated the procedure well. After recovery from anesthesia, the intensity and frequency of uterine contractions increased, reaching an activity of 300 Montevideo Units.15 Even with a dose of 6 pg per minute of
down
to the
deridual
layer;
the
membranes
are
874
Seelen
et al.
Fig. 2. (I, A thin near
the marsin
polyl.inylcathetrr of the plarrnta.
is insert4 into ‘1 small fetal h. Closr-up taken post partrlllr.
100 200 300 Fig. 3. Change during trchn&rx
the
400
\.?in
500 600
on thr
chnrionic
plate
700ml
in the values of percentage of fetal hemoglobin, hematocrit. and bilirubin exchange transfusion. The estimations of thr acid-base status with th? Astrup Ifa ml. revralt~d normal \YllLl~S. in the first sampk and nftrr vxchan.zin4
Volume Sumber
95 6
Exchange
Table I. Blood transfusion
analysis of the child and after birth
before
At
Before
19 hours after exchange transfusion at birth
ex-
change transfusion Blood group Hemoglobin (Gm.%) Hematocrit (vol.% ) Leukocytes (mm.5) Normoblast/lOO leukocytes Reticulocytes (% ) Coombs test Antibody titer Saline method Indirect antiglobulin method Bilirubin (mg. % ) Direct Total Total protein (Gm.%) Hemoglobin (F % )
Cc-25’6 activity video
A
A
cde/CDe
cde/cde
7.0 21.5 4400
15.2 48.5 3900
25 500 +++
40 40 Negative
Negative
Negative
l/128
l/128
0.8 4.6 3.8
combined with propranolol,‘r could only be lowered Units.
5.43
the uterine 100 Monte-
Eighteen hours after the operation the cervix was completely effaced and 5 cm. dilated. The infusion of Cc-25 was stopped and amniotomy performed. A boy weighing 1,700 grams, Apgar score 8, was born spontaneously 30 minutes thereafter. The liver was enlarged, reaching the pelvic brim. The spleen could be palpated 3 cm. under the costal margin. The analysis of the cord blood is summarized in Table I. Two hours later, the placenta had to be removed manually. During this procedure, the incision site in the uterine wall was found to he intact. The child did fairly well but had to have three exchange tranfusions with 500 ml. blood because of hyperhilirubinemia.
Comment An
intrauterine
exchange
transfusion
875
sac, the chances of starting labor are considerably reduced. Our method insures an intact amniotic sac. The experiments on pregnant monkeys and our experience in the case here described have convinced us that the amnion is a strong tissue resistant to traction. The
tient
10
to
in utero
loss
of amniotic
fluid
in this
case
was
not caused by rupture of the amnion but by pre-existing puncture holes. We do not doubt that if we had tried to gain access to the chorionic plate outside this “danger area,” the volume of the amniotic sac could have been maintained and, correspondingly, the chance of prematurely induced labor smaller. As to the premature birth in our case, it should be mentioned that our pa-
0.6 4.2
100
transfusion
has
to be preferred to an intrauterine intraabdominal infusion, as has been emphasized by Freda and Adamsons.? The risk of the former procedure is an unwanted induction of labor. However, if the operation can be performed without rupture of the amniotic
had
experienced
uterine
contractions
several weeks previously and also for a couple of hours on the evening before the operation. One might suggest that a “proneness” to labor existed. Apart from this, it is clear that any manipulation of a pregnant uterus involves the risk of starting labor. The purpose of intrauterine exsanguination is to obtain a high concentration of erythrocytes that cannot be attacked by the circulating antibodies. The exsanguination in our case was performed with 670 ml. normal donor blood, estimating the total fetal circulatory volume to be about 200 ml. However, assuming the fetal circulation had a fixed volume, it is quite clear that the desired concentration of erythrocytes can be reached more easily by using concentrated blood. The amount of blood needed can be easily calculated. Then it can be postulated that in performing exsanguination with blood of a hematocrit value of 60 to 70 volumes per cent with an amount of twice the assumed volume of the fetal circulation, the result would be a hematocrit value in the fetal circulation of about 50 volumes per cent, the fetal hemoglobin being less than 10 per cent of the total hemoglobin. However, as the changing content of the plasma proteins will influence the fetal blood volume and, therefore, the concentration of the erythrocytes, the fetal circulation cannot be considered as a fixed volume.
876
Seelen
Further dynamics
et al
investigation of the fetal hemowill be needed before the ideal
conditions tion will
for an intrauterk be known.
ctssanquina-
REFERENCES
1. 2. 3.
4.
5.
6.
7.
8. 9.
10.
Liley, Freda,
A. W.: Brit. M. J. 2: 1107, 1963. V. J., and Adamsons, K.: AM. J. OBST. & GYNEC. 89: 817, 1964. Stolte, L. A. M., Seelen, J. C., Kessel van, H.I.A.M., and Zonderland, J. B. M.: Nederl. tijdschr. verlosk. en gynaec. 63: 213, 1963. Kessel van, H., Stolte, L. A. M., and Seelen, J. C.: Acta physiol. et pharmacol. neerl. 12: 167, 1963. Seelen, J. C., Kessel van, H., and Stolte, L. A. M.: Acta physiol. et pharmacol. neerl. 12: 177, 1963. Kessrl van, H., Knipscheer, R., Seelen, J. C., and Stolte, L. A. M.: Nederl. tijdschr. verlosk. en gynaec. 64: 266, 1964. Leusden van, H. A. I. M., Stolte, I,. A. M.. Seelen, J. C., and Kessel van, H.: Nederl. tijdschr. verlosk. en gynaec. 64: 326, 1965. Knipscheer, R.: Megaloblastaire anaemie in de zwangerschap, Thesis, Nijmegen, 1965. Kock. H. C. L. V., Reichert, A., Stolte, I,. A. M.. Kessel van, H., and Seelen, J. C.: Acta physiol. et pharmacol. necrl. 13: 363, 1965. Reynolds, S. R. M., Paul, W. M.. and Hug-
11. 12. 13.
14.
15.
16.
17.
gett, A. St. G.: Bull. Johns Hopkins Hosp. 95: 256, 1954. Seelen, J. C.: Nederl. tijdsrhr. verlosk. en gynaec. 61: 337, 1961. Seelen, J. C.: Nederl. tijdschr. verlosk. en gynaec. 62: 86, 1962. Kessel van, H., and Kock, H. C. I,. V.: Nederl. tijdschr. verlosk. en gynacc. 64: 151, 1964. Eskes, T. K. A. B.: De druk in de baarmoeder voor, tijdens en na de baring, Thesis, Nijmegen, 1962. Caldeyro-Barcia, R., Sica-Blanco, Y., Poseiro, J. J., Gonzales-Pan&a, V. H., MendtzBauer, C., Fielitz, C., Alvarez, H.. Pose, S. V., and Hendricks, C. H.: J. Pharmacol. & Exner. Therao. 121: 18. 1957. Stolte,‘L., Eskes, *T., Seelen, J., Moed, H. D., and Vogelsang, C.: AM. J. OBST. & GYNEC. 92: 865, 1965. Eskes, T., Stolte, L., Seelen, J.. Moed, II. D., and Vogelsang. C.: AM. J. OBST. 8r GYNEC. 92: 871, 1965.
J.
of vessels
SEELEN,
H.
VAN
T.
ESKES,
on the fetal
placenta
M.D. KESSEL.
M.D.
M.D.
H.
VAN
LEUSDEN,
J.
BEEN,
M.D.
J.
EVERS,
I.
VAN
L.
PEETERS,
M.D.
W.
VAN
VELDEN,
F.
side of the human
in utero
M.D.
M.D. GENT, DER
M.D. M.D
ZONDERLAND
Nijmegen,
The
Netherlands
LILEY,’ in 1963, introduced the intrauterine intra-abdominal infusion of concentrated blood in cases of threatening intrauterine fetal death clue to erythroblastosis fetalis. An intrauterine exchange transfusion, however, would seem the treatment of choice in these cases. Freda and Adamsons’ succeeded in exchanging fetal blood through the femoral artery. A disadvantage of this method is the necessity of rupturing the membranes with increased risk of immature or premature labor. The present report gives a method for intrauterine exchange transfusion with intact amniotic sac. The idea for this method crossed our mind during intrauterine operations on pregnant monkeys,“-” performed according to the technique of Reynolds, Paul, and Huggett. l’) It appeared to be possible to reach th? vessels of the fetal side of the
From the University Department Obstetrics and Gynecology, St. Rndboud Hospital.
placenta and to cannulate these ves,sels with free flow, without any damage to the amniotic sac. Case
report
Mrs. v. A-D., a 29-year-old gravida 6, para 3, was a sensitized Rh-negative mother (A cde/ cde) and who was sent to us for the first time in the twenty-eighth week of her pregnancy. She had a bad obstetrical history; the only child alive has serious neurological damages. Pregnancy proceeded normally although she had to be admitted because of premature uterine contractions. With the saline and the indirect antiglobulin methods, titers of rhesus antibodies (anti-D) of l/l and 1,312, respectively, were observed. From rhesus genotyping of the former children it could be derived that the husband of our patient was homozygous for the D-antigen (B, CDe/cDe) The findings in the amniotic fluid indicated that the fetus was suffering from a severe form of hemolytic disease. lx, I* In the thirty-fourth week of pregnancy, we concluded that fetal death was impending. At that moment, we had to choose between induction of labor and an attempt at intrauterine exchange transfusion. The fact that her last
of
872
Volume Number
95 6
Exchange
prematurely born child (36 weeks) died of respiratory distress made us prefer the latter procedure. The placenta was localized with IsrI-albumin13 and was found to be situated in the right front part of the uterus. Median line laparotomy was performed under general anesthesia. Neither inspection nor palpation or transillumination with a strong fiber light source revealed the exact location of the placental margin. Guided by the radioisotopic placental localization, a 3 cm. incision was made in the myometrium high in the lower part of the uterus just left of the midline and carried down to the decidual layer (Fig. 1). Blunt dissection with two nontoothed forceps separated the decidua and chorion easily from the amnion. The margin of the placenta could be reached easily by the exploring finger between the amnion and the chorion at a distance of 2 to 3 cm. to the right of the incision. In further loosening the chorion from the amnion, again only using the finger, a totally unexpected complication took place. We arrived in the area of the former transabdominal amniotic puncture sites and, at several small spouts of fluid this moment, through these puncture holes occurred. Obviously, the closure of these holes is accomplished only by the chorion and,/or decidual tissue and not by healing of the amnion itself. Surgical closure of these holes seemed impossible. Ring-
Fig. 1. The bulging.
myometrium
has been
incised
transfusion
in utero
873
shaped forceps were placed upon the myometrium close to the placental edge, and the amniotic sac was further separated from the chorionic plate. By manipulating the forceps, the chorionic plate with its vessels was brought into view. A small vein near the margin was cannulated over a length of 10 to 12 cm. with an 8 inch polyvinyl catheter (i.d. 0.015) which was fixed in the vein by atraumatically suturing the vein to the chorionic plate (Fig. 2, a and b j. Blood was obtained easily. The results of thv immediately performed analysis are given in Table I. An exchange transfusion of 670 ml. of heparinized fresh A cde/cde blood was prrformed without any difficulty by removing and replacing 8 ml. of blood at a time during 110 minutes. Data relevant to this exchange transfusion are given in Fig. 3. The catheter was then removed and the vessel tied. The myomrtrium was closed in two layers. The uterus seemed to be contractile. An open-tip saline filled catheter was introduced through an amniotic puncture to record intrauterine pressure.l* Contractions of 15 mm. Hg with a frequency of 2.0 contractions per 10 minutes were observed. Both mother and fetus tolerated the procedure well. After recovery from anesthesia, the intensity and frequency of uterine contractions increased, reaching an activity of 300 Montevideo Units.15 Even with a dose of 6 pg per minute of
down
to the
deridual
layer;
the
membranes
are
874
Seelen
et al.
Fig. 2. (I, A thin near
the marsin
polyl.inylcathetrr of the plarrnta.
is insert4 into ‘1 small fetal h. Closr-up taken post partrlllr.
100 200 300 Fig. 3. Change during trchn&rx
the
400
\.?in
500 600
on thr
chnrionic
plate
700ml
in the values of percentage of fetal hemoglobin, hematocrit. and bilirubin exchange transfusion. The estimations of thr acid-base status with th? Astrup Ifa ml. revralt~d normal \YllLl~S. in the first sampk and nftrr vxchan.zin4
Volume Sumber
95 6
Exchange
Table I. Blood transfusion
analysis of the child and after birth
before
At
Before
19 hours after exchange transfusion at birth
ex-
change transfusion Blood group Hemoglobin (Gm.%) Hematocrit (vol.% ) Leukocytes (mm.5) Normoblast/lOO leukocytes Reticulocytes (% ) Coombs test Antibody titer Saline method Indirect antiglobulin method Bilirubin (mg. % ) Direct Total Total protein (Gm.%) Hemoglobin (F % )
Cc-25’6 activity video
A
A
cde/CDe
cde/cde
7.0 21.5 4400
15.2 48.5 3900
25 500 +++
40 40 Negative
Negative
Negative
l/128
l/128
0.8 4.6 3.8
combined with propranolol,‘r could only be lowered Units.
5.43
the uterine 100 Monte-
Eighteen hours after the operation the cervix was completely effaced and 5 cm. dilated. The infusion of Cc-25 was stopped and amniotomy performed. A boy weighing 1,700 grams, Apgar score 8, was born spontaneously 30 minutes thereafter. The liver was enlarged, reaching the pelvic brim. The spleen could be palpated 3 cm. under the costal margin. The analysis of the cord blood is summarized in Table I. Two hours later, the placenta had to be removed manually. During this procedure, the incision site in the uterine wall was found to he intact. The child did fairly well but had to have three exchange tranfusions with 500 ml. blood because of hyperhilirubinemia.
Comment An
intrauterine
exchange
transfusion
875
sac, the chances of starting labor are considerably reduced. Our method insures an intact amniotic sac. The experiments on pregnant monkeys and our experience in the case here described have convinced us that the amnion is a strong tissue resistant to traction. The
tient
10
to
in utero
loss
of amniotic
fluid
in this
case
was
not caused by rupture of the amnion but by pre-existing puncture holes. We do not doubt that if we had tried to gain access to the chorionic plate outside this “danger area,” the volume of the amniotic sac could have been maintained and, correspondingly, the chance of prematurely induced labor smaller. As to the premature birth in our case, it should be mentioned that our pa-
0.6 4.2
100
transfusion
has
to be preferred to an intrauterine intraabdominal infusion, as has been emphasized by Freda and Adamsons.? The risk of the former procedure is an unwanted induction of labor. However, if the operation can be performed without rupture of the amniotic
had
experienced
uterine
contractions
several weeks previously and also for a couple of hours on the evening before the operation. One might suggest that a “proneness” to labor existed. Apart from this, it is clear that any manipulation of a pregnant uterus involves the risk of starting labor. The purpose of intrauterine exsanguination is to obtain a high concentration of erythrocytes that cannot be attacked by the circulating antibodies. The exsanguination in our case was performed with 670 ml. normal donor blood, estimating the total fetal circulatory volume to be about 200 ml. However, assuming the fetal circulation had a fixed volume, it is quite clear that the desired concentration of erythrocytes can be reached more easily by using concentrated blood. The amount of blood needed can be easily calculated. Then it can be postulated that in performing exsanguination with blood of a hematocrit value of 60 to 70 volumes per cent with an amount of twice the assumed volume of the fetal circulation, the result would be a hematocrit value in the fetal circulation of about 50 volumes per cent, the fetal hemoglobin being less than 10 per cent of the total hemoglobin. However, as the changing content of the plasma proteins will influence the fetal blood volume and, therefore, the concentration of the erythrocytes, the fetal circulation cannot be considered as a fixed volume.
876
Seelen
Further dynamics
et al
investigation of the fetal hemowill be needed before the ideal
conditions tion will
for an intrauterk be known.
ctssanquina-
REFERENCES
1. 2. 3.
4.
5.
6.
7.
8. 9.
10.
Liley, Freda,
A. W.: Brit. M. J. 2: 1107, 1963. V. J., and Adamsons, K.: AM. J. OBST. & GYNEC. 89: 817, 1964. Stolte, L. A. M., Seelen, J. C., Kessel van, H.I.A.M., and Zonderland, J. B. M.: Nederl. tijdschr. verlosk. en gynaec. 63: 213, 1963. Kessel van, H., Stolte, L. A. M., and Seelen, J. C.: Acta physiol. et pharmacol. neerl. 12: 167, 1963. Seelen, J. C., Kessel van, H., and Stolte, L. A. M.: Acta physiol. et pharmacol. neerl. 12: 177, 1963. Kessrl van, H., Knipscheer, R., Seelen, J. C., and Stolte, L. A. M.: Nederl. tijdschr. verlosk. en gynaec. 64: 266, 1964. Leusden van, H. A. I. M., Stolte, I,. A. M.. Seelen, J. C., and Kessel van, H.: Nederl. tijdschr. verlosk. en gynaec. 64: 326, 1965. Knipscheer, R.: Megaloblastaire anaemie in de zwangerschap, Thesis, Nijmegen, 1965. Kock. H. C. L. V., Reichert, A., Stolte, I,. A. M.. Kessel van, H., and Seelen, J. C.: Acta physiol. et pharmacol. necrl. 13: 363, 1965. Reynolds, S. R. M., Paul, W. M.. and Hug-
11. 12. 13.
14.
15.
16.
17.
gett, A. St. G.: Bull. Johns Hopkins Hosp. 95: 256, 1954. Seelen, J. C.: Nederl. tijdsrhr. verlosk. en gynaec. 61: 337, 1961. Seelen, J. C.: Nederl. tijdschr. verlosk. en gynaec. 62: 86, 1962. Kessel van, H., and Kock, H. C. I,. V.: Nederl. tijdschr. verlosk. en gynacc. 64: 151, 1964. Eskes, T. K. A. B.: De druk in de baarmoeder voor, tijdens en na de baring, Thesis, Nijmegen, 1962. Caldeyro-Barcia, R., Sica-Blanco, Y., Poseiro, J. J., Gonzales-Pan&a, V. H., MendtzBauer, C., Fielitz, C., Alvarez, H.. Pose, S. V., and Hendricks, C. H.: J. Pharmacol. & Exner. Therao. 121: 18. 1957. Stolte,‘L., Eskes, *T., Seelen, J., Moed, H. D., and Vogelsang, C.: AM. J. OBST. & GYNEC. 92: 865, 1965. Eskes, T., Stolte, L., Seelen, J.. Moed, II. D., and Vogelsang. C.: AM. J. OBST. 8r GYNEC. 92: 871, 1965.