- Email: [email protected]
Postpartum hemorrhage
Postpartum MICHAEL Jackson,
hemorrhage
NEWTON,
M.D.
Missis&@&
T H E A M o u N T of blood lost during and immediately after delivery remains an important clinical problem for three reasons. First, severe bleeding may occur suddenly and unexpectedly and transform a normal delivery into a catastrophe. Moreover, hemorrhage is still a leading cause of maternal death. For example, in Mississippi, during the years 1959 through 1963, 72 of 252 (29 per cent) maternal deaths studied by the State Medical Association’s Committee on Maternal and Child Care were found to be due to hemorrhage (Table I). Second, moderate amounts of blood lost during delivery may complicate the puerperium and debilitate the mother so that she is not in optimum condition for the stress of caring for her newborn baby, as well as her husband and other children. Third, there is still need for finding new, safe, and effective ways of preventing and treating obstetrical hemorrhage. Transfusions, ergot derivatives, and oxytocin have, indeed, saved many lives, but all have some disadvantages. This report covers a series of investigations in the field of obstetrical blood loss. First, we spent some time developing and determining the accuracy of our method of measurement. Second, we studied blood loss in a group of normal patients who received no oxytocics unless excessive bleeding occurred. From the Defiartment Gynecology, University School of Medicine.
of
Obstetrics
Finally, we tested the effect of synthetic oxytocin and sparteine sulfate on measured blood loss. Methods
of
measurement
The acid hematin spectrophotometric method was chosen for determining blood loss. Briefly, this involves the collection of liquid material and pads, sponges, etc., containing blood in a solution of O.lN hydrochloric acid. By this means, the hemoglobin is converted into acid hematin. Appropriately diluted samples of this fluid and of the patient’s blood drawn at the same time are then read in the Klett-Summerson colorimeter. Blood loss can then be calculated by a simple formula.l~ * The accuracy of the method was tested by a series of in vitro experiments. Under conditions simulating delivery, it was possible to recover an average of 97.9 per cent of the blood used when citrate had been added and 88.5 per cent when the blood was fresh. Using perineal pads to simulate postpartum conditions it was possible to recover an average of 92.9 per cent of the blood used. It is of interest that a similarly high degree of accuracy has recently been reported by Miller.3 The value of accurate measurement of blood loss compared with the usual practice of estimation became apparent as the study
and
of Mississippi
Table I. Maternal
These studies were supported in part by grants from Sandoz Pharmaceuticals, Division of Sandoz, Incorporated, Hanover, New Jersey, and from Ayerst Laboratories, New York, New York.
Maternal Year
Presented by invitation at the Seventy-sixth Annual Meeting of the American Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Sept. 9-11, 1965.
711
1
Total
deaths deaths 1
from due No.
hemorrhage to hemorrhage )
%
1959 1960
52 58
19 14
37 24
1962 1961 1963
53 48 41
14 10 15
;ii 37
712
March 1, 1966 Am. J. Obst. L Gynec.
Newton
proceeded. Thus, in 100 patients the mean error of estimation as compared with measurement was 46 per cent, even allowing for the fact that those making the estimation had been sensitized by the conduct of the investigation. More importantly, estimations tended to be low when the blood loss was high-20 per cent low when the loss was between 400 and 499 C.C. and 34 per cent low when the loss was 500 C.C. or more. Control patients. One hundred and five patients were studied. Twenty-eight were primiparas and 77 were multiparas. They were included only if they were at 36 weeks of gestation or more, had had no serious complications of pregnancy, and were expected to have no serious difficulties during labor and delivery. During the period of study, all patients who met the criteria were included, unless the labor was so rapid or the delivery suite so busy that it was impossible to collect the samples accurately. Patients were managed during labor and delivery according to the usual practices of the department. No oxytocics were given these patients unless, in the opinion of the resident in charge of the delivery suite, bleeding was sufficient to require treatment. In this case, synthetic oxytocin, 20 units in
Table II. Obstetrical
blood
1,000 cc. 5 per cent dextrose in water. was given intravenously. In each patient, blood loss was measured for three periods (1) while she was on the delivery table (on-table loss), (2) for the first hour after she was removed from the delivery table and while she was still in the delivery suite (post-table loss), and (3) during the remainder of the first 24 hours post partum (1 to 24 hour loss). Large individual variations in blood loss were apparent among the normal patients (Table II). As an example, the on-table loss in multiparas showed a very large standard deviation and a wide range. Further analysis of these variations resulted in some interesting observations. The large majority of the losses were below 300 C.C. (in 49 of 77, 64 per cent). Only 4 were between 300 C.C. and 400 C.C. and 7 between 400 C.C. and 500 cc., while 17 patients (22 per cent) had losses of over 500 c.c., a figure which is normally considered an obstetrical hemorrhage. The same trend was noted in the post-table loss in multiparas. Sixty-three patients (82 per cent) lost under 100 cc., one lost between 100 C.C. and 149 c.c., 3 lost between 149 C.C. and 200 cc., and 10 lost over 200 C.C. At the one to 24 hour period this tendency for certain women to have excessive losses was much less marked. Here 66 of 73 multiparas (90 per cent) lost less than 100 cc. Only 3 lost more than 200 C.C. The on-table loss appeared to be considerably higher in primiparas than in multiparas but this difference was not statistically significant owing to the wide individual variations and the small numbers of patients, However, primiparas lost significantly less blood than multiparas in the post-table and
loss in normal
women Primiparas
Multiparas
No.~bl+%JL On-table Post-table 1 to 24 hours
28 28 27
No.~bl;.~
625+337 20+ 17 462 56
77 77 73
3142310 93 2 155 87 + 139
post partum
Table III. Effect of synthetic
oxytocin
on blood
loss
Primiparas
Multiparas
Control
On-table Post-table 1 to 24 hour
post partum
Oxytocin
No.
Mean blood loss (CL.)
28 28 27
625 20 46
No. 13 13 7
Control
Mean blood loss (C.C.) 401 19 28
No. :: 73
Oxytocin
Mean blood loss (Cd.)
No.
Mean blood loss (C.C.)
314 93 87
37 37 26
325 43 142
Volume Number
94 5
Postpartum
in the 1 to 24 hour periods (p = lessthan 0.01 in both cases). In the post-table period this may have been due to the fact that more primiparas had received intravenous oxytocin to control excessive bleeding. Effect of synthetic oxytocin on blood loss. Fifty patients, 13 primiparas and 37 multiparas, received synthetic oxytocin, 10 units intramuscularly, after the delivery of the placenta and 10 units intramuscularly every 6 hours thereafter. They were selected by the same criteria as the control patients and were alternated with them. Thy received the same type of obstetrical management. No significant differences in blood loss at any of the three periods studied were noted between the patients receiving synthetic oxytocin and the controls (Table III). However, the beneficial effect of synthetic oxytocin upon blood losswas more clearly shown by the smaller number of patients requiring additional oxytocics to control excessive bleeding immediately after delivery (Table IV). These differences were highly significant statistically for both primiparas and multiparas (p = lessthan 0.01). Effect of sparteine sulfate on blood loss. Forty-eight patients (11 primiparas and 37 multiparas) received sparteine sulfate 150 mg. intramuscularly after the delivery of the
16 13
12 0
58 36
713
baby’s anterior shoulder and 150 mg. intramuscularly every 4 hours thereafter. They were chosen for inclusion in the study by the same criteria used for the control patients and were randomly selected for the administration of sparteine sulfate. No significant differences in blood loss were noted between the patients receiving sparteine sulfate and the controls (Table V). However, sparteine sulfate was also shown to be an effective oxytocic agent by the fact that a smaller number of the patients receiving it required additional oxytocics to control hemorrhage (Table VI) . Again these differences were highly significant statistically for both primiparas and multiparas (p = lessthan 0.01). Comment
In these studies the mean total loss of blood during and shortly after delivery (ontable and post-table losses) was 470 cc. Allowing for a measurement error of 10 per cent and for 60 C.C. contained in the average placenta,4 a total blood loss of 577 C.C.is obtained. This figure agreesfairly well with that determined by Pritchard5 using chromium-labeled red cells. However, the actual loss by the average woman was probably more than this, since excessiveloss was controlled by giving additional oxytocics. Our data do not provide any explanation for the marked individual differences in blood loss. All the patients studied were supposedly normal although variations in general health or nutritional status might have been present. Furthermore, review of the 41 multiparas who lost a total of more than 500 C.C.blood during the on-table and post-table periods combined showed that
Table IV. Additional oxytocics in patients receiving synthetic oxytocin
No oxytocic Synthdtic oxytocin
hemorrhage
19 1
Table V. Effect of sparteine sulfate on blood loss Primiparas
Multiparas
Control
No. On-table Post-table 1 to 24 hour
postpartum
28 28 27
Sparteine
Mean blood loss (c.c.) 625 20 46
No. 11 11 11
Sfiarteine
Control
Mean blood loss (c.c.) 599 46 69
No. 77 77 73
Mean blood loss (c.c.) 314 93 87
No. 37 37 36
Mean blood loss (CL.) 300 61 99
714
March 1, 1966 Am. J. Obst. & Gynec.
Newton
Table
VI. Additional
receiving
sparteine
oxytocics sulfate Additional
Patients receiving delivery
Primijmras at
Not given
No oxytocic Sparteine sulfate
16 10
I Given 12 1
in patients
oxytocics Multiparas Not I given 58 35
I Given 19 2
there were no differences between them and the remainder as far as age, parity, length of labor, analgesia, anesthesia, method of delivery, or trauma at delivery were concerned. Of the two oxytocic agents used, synthetic oxytocin needs little discussion. It has been established as a satisfactory drug whose main disadvantage is that it takes several minutes to act if given intramuscularly. Sparteine Its sulfate deserves additional comment. main reported use has been to stimulate labor but it has not been used much post partum. Our experience indicates that it is an effective oxytocic agent when used in this manner. No untoward side reactions and specifically no retained placentas were noted. Hypertension was not found, although the mean blood pressure of the control group fell a little more postpartally than that of the group receiving sparteine. Summary
and
conclusions
1. Blood loss was measured during delivery, in the first hour after removal from
the delivery table and in the remainder of the first 24 hours post partum in 203 obstetrical patients by the acid hematin spectrophotometric method. 2. In 105 normal patients who received no oxytocics unless bleeding was excessive the mean total on-table and post-table loss was 470 cc. During the rest of the first 24 hours after delivery the mean loss was 76 cc. Multigravidas lost significantly more blood than primigravidas during the posttable and 1 to 24 hour periods. Wide individual variations in blood loss were noted. No consistent cause for this could be found. 3. Blood loss was measured in 50 normal patients who were given 10 units of synthetic oxytocin intramuscularly after the delivery of the placenta and in 48 patients who were given 150 mg. sparteine sulfate at the delivery of the baby’s anterior shoulder. There were no significant differences between either of these two groups of patients and the controls in measured blood loss in any of the three periods studied. 4. Both synthetic oxytocin and sparteine sulfate were found in this study to be effective oxytocic agents in that a significantly smaller number of patients in each treated series than of those in the control series required additional oxytocics for the management of hemorrhage. 5. No special advantage was found for continuing the use of oxytocics routinely in the puerperium unless they were indicated by excessive bleeding
REFERENCES
1.
2. 3.
Newton, M., Mosey, L. M., Egli, G. E., Gifford, W. B., and Hull, C. T.: Obst. & Gynec. 17: 9, 1961. Newton, M., and Bradford, W. M.: Obst. & Gynec. 17: 229, 1961. Miller, R. L.: Obst. & Gynec. 25: 553, 1965.
4. 5.
Newton, M., and Moody, Gynec. 18: 305, 1961. Pritchard, J. A., Baldwin, C., and Wiggins, K. M.: GYNEC. 84: 1271, 1962.
A.
R.:
Obst.
&
R. M., Dickey, AM. J. OBST.
J. &
Discussion DR. W. NORMAN THORNTON, JR., Charlottesville, Virginia. Hemorrhage as a leading cause of maternal death is truly a tragedy in modem obstetrics. It will remain one of the leading causes of maternal death until State Health
Departments to maintain
stetrical
require adequate
rural maternity hospitals supplies of blood for ob-
emergencies.
now must depend 50 miles away.
Some of these small units on
blood
banks
some
30
to
Volume !?4 Number 5
This is the fourth report by Dr. Newton and his associates which clearly indicates that the blood loss associated with delivery and the immediate puerperium is significant and much greater than the inaccurate estimates which we usually employ. The mean total loss, including that contained in the placenta, of 577 ml. is a significant amount and may well account for some of the anemias so commonly seen in the grand multipara who frequently enjoys only a few months between pregnancies. Dr. Newton’s measured loss is in agreement with that reported by Pritchard and the accuracy of the method has recently been confirmed by Miller. The author states that he is unable to explain the marked individual variations in blood loss, since in his series, there were no significant differences in measurable factors. One wonders if a more meticulous assessment of the vagina, cervix, and uterus might not have given some answer to these individual variations in blood loss. Recently, we have had the opportunity to review the findings in 1,000 consecutive explorations of the uterus, cervix, and vagina immediately following delivery of the placenta. In spontaneous deliveries, unsuspected cervical lacerations were found in 4.73 per cent and vaginal lacerations in 4.1 per cent of the patients. In forceps deliveries, cervical lacerations were SUStained in 13.3 per cent and vaginal lacerations in 14.9 per cent of the patients. In addition to these sources of blood loss, placental fragments were found in 1 per cent of the uteri explored. Dr. Newton’s clinical observation that sparteine sulfate is an effective oxytocic agent confirms some observations made in our laboratories. In vitro assessment of isolated human myometrial strips excised from gravid uteri show that increasing concentrations of sparteine sulfate result in a progressive increase in frequency of contractions as well as tone associated with a progressive decrease in contractile waves. The more striking observation and one which may be associated with a reduction in blood loss was noted in the contractile response of strips of human uterine artery on exposure to sparteine sulfate. This resulted in a marked increase in tone and frequency of contractions whereas oxytocin produced no appreciable change in contractile response. Additional in vitro observations indicate that the action of sparteine sulfate on isolated human uterine artery strips is similar to that of ergonovine maleate. The author is to be congratulated for presenting information which indicates that both spar-
Postpartum
hemorrhage
715
teine sulfate and synthetic oxytocin are effective uterine stimulants, and that a significantly smaller number of patients receiving either of these agents required additional oxytocics for the control of hemorrhage. DR. FRANK E. WHITACRE, Nashville, Tennessee. Dr. Newton’s figures on maternal deaths in the State of Mississippi were interesting. In Tennessee during the same period of time, 1959 through 1963, we had 407,323 births. There were 190 maternal deaths and of these 44 or 23.1 per cent were due to hemorrhage. Fifty or 26.3 per cent were due to toxemia of pregnancy and 40 or 21.1 per cent were due to infection. It is commonly said that these three major causes of maternal deaths are preventable, but perhaps many of you would agree with me that this is not always the case. Dr. Newton’s method of measuring blood loss is certainly an improvement over inaccurate estimation. In the group of normal patients who received no oxytocics unless bleeding was excessive, the total blood loss of 470 C.C.is higher than I would expect. The numerous causes of postpartum bleeding have been analyzed many times. We feel, however, that two of the causes are sometimes ignored. First, unwise conduct of the third stage which usually means giving the placenta insufficient time to separate and ignoring the principle to never press on a relaxed uterus. The second common cause is a foreign body in the uterus and an ordinary blood clot is much more frequent than retained secundines. Although the intravenous drip using dilute oxytocin was at first used as a method of induction, and/or stimulation of labor, the method is also most useful in controlling the bleeding of patients with incomplete abortion and bleeding in the postpartum period. I would expect it to be superior to the use of sparteine sulfate because after intramuscular injection, a drug is not as immediately effective as by intravenous injection and its action cannot be controlled as well. I would like to call attention to the effect of bleeding in late pregnancy on the baby. An estimation would indicate that at 28 weeks the fetus has about 85 C.C. of blood and weighs about 2 pounds, 4 ounces. The amount of blood and the body weight will be approximately tripled by the thirty-ninth week; therefore, any given amount of blood lost by the fetus at 28 weeks is three times as great as at term. Under the direction of Dr. Everett Clayton at the Nashville Metropolitan General Hospital,
716
Newton
we perfected a method of identification of fetal erythrocytes in the maternal circulation and then on the suggestion of Dr. Edith Potter, we have been determining the amount of fetal blood loss in third trimester vaginal bleeding. This work will appear in the literature in the near future. DR. T. W. MCELIN, Evanston, Illinois. The relatively unchanging percentage of maternal deaths due to hemorrhage emphasize the need for continued vigorous research and more intensive patient care. Evidence for this is Dr. Newton’s Table I showing that 37 per cent of all maternal deaths in Mississippi in 1959 were due to hemorrhage, and that the figure in 1963 was again 37 per cent. My remarks will be directed to four points: 1. General agreement is to be anticipated with two of Dr. Newton’s conclusions: (A) The greater accuracy of measurement of blood loss compared with estimation is apparent; and (B) There is no special advantage in the routine usage of oxytocics in the postpartum period. 2. I would appreciate further information regarding the definition of “normal patients.” I about the “usual” am, of course, wondering variables of delivery: spontaneous versus operative delivery, the type of episiotomy, presence or absence of lacerations, the performance or nonperformance of uterine exploration, etc. We are told only that comparisons of this type were made in 41 patients who had a blood loss in excess of 500 cc. This information looms important as we have already been asked to analyze variables, for example, of the order of 314 + 310 cc. measured blood loss in one instance or 93 + 155 cc. in another instance. 3. 1 was interested in the author’s selection of routine dosages of synthetic oxytocin and sparteine sulfate given at the time of delivery in his study of measured blood loss in two separate groups of patients. Ten units of intramuscular synthetic oxytocin was administered after delivery of the placenta to one group-a dosage over 20 times that which might be given as an intramuscular oxytocic dosage during labor. Contrariwise, 150 mg. of sparteine sulfate was administered after delivery of the anterior shoulder to a comparable group. This is, of course, a recommended dosage of this drug for oxytocic purposes in labor. The conclusion is then presented, “there were no significant differences between either of these two groups of patients and the controls in measured blood loss.” A vastly greater amount of oxytocin as compared to sparteine sulfate, relative to the usual ante-
March 1, 1966 Am. J. Obst. % Gynec.
partum dose, was given and, hence, I question the validity of this particular conclusion. 4. Comment should be made on the conclusion that there is no difference in the postpartum blood loss of those patients given oxytocin and sparteine sulfate at the time of delivery. If indeed this is so, I should like to record my preference for oxytocin. Despite my significant enthusiasm for sparteine sulfate as an oxytocic agent, based on our extensive and published experience from Evanston Hospital, I must acknowledge that the intramuscular administration of certain dosage forms of sparteine sulfate is often moderately and, occasionally, severely uncomfortable for the patient. DR. CLARENCE BRISCOE, Philadelphia, Pennsylvania. Dr. Newton has correctly emphasized the impact of blood loss on maternal mortality and debility. The attack on the problem should begin with the antenatal administration of iron. Unfortunately, high hemoglobin levels do not guarantee adequate iron reserves; hence, iron administration should be routine, not only during pregnancy but following it as well. It was surprising that little difference was noted between oxytocin and sparteine sulfate. My romance with sparteine was early and disenchanting. It is an unpredictable drug, producing tetanic contractions in one uterus or none at all in another. Using a Pastore collecting tray to measure blood loss, we have found distinct advantage in the intravenous injection of ergot at the birth of the shoulders. Trapped placentas, increasing the incidence of manual removal, is a complication of this method. Without this prophylactic dose, the uterus, often flabby, could be made to contract by direct intrauterine injection of ergonovine, either transabdominally or transvaginally through the anterior fornix. Some of our students may practice in conmmunity hospitals without house or nursing staff available for venipuncture and they should be aware of this technique. By packing the upper vagina, blood loss during slow intern episiotomy repairs was measured and found to average 100 ml., reaching 500 ml. in one instance. Since 1948, I have practiced planned deliberate exploration of each postpartum uterus. Retained secundines were found in 4 per cent of our cases. Uterine anomalies, submucous myomas, thin scars, clots and accessory placental lobes are occasionally uncovered. An atonic uterus is immediately discovered and massaged.
Volume 94 Number 5
Blood loss is decreased and febrile morbidity is lower while postpartum hemoglobin levels are higher than in the unexplored cases. DR. NEWTON (Closing). In reply to Dr. Thornton, we have looked at the figures for maternal deaths due to hemorrhage in Mississippi. By 1961 a steady decrease had become apparent, possibly due to the fact that the blood bank situation in the state had improved. In 1963, however, deaths from hemorrhage again increased and we were somewhat discouraged. We have not routinely explored the uterus, as suggested by Drs. Thornton and Briscoe, and, therefore, cannot make any statements about this. I am interested in the arterial tone studies with sparteine sulfate, mentioned by Dr. Thomton. We have been concerned lest sparteine sulfate produce an elevation of blood pressure in some patients such as occurs occasionally with ergot derivatives. We have not been able to prove that this happens. In none of the patients given sparteine sulfate was there any startling rise in blood pressure, but, the overall fall in blood pressure post partum, based on means, was somewhat less than in the control group. With regard to the percentage of maternal deaths due to hemorrhage, it is evident, in reply to Dr. Whitacre, that in Tennessee blood banks are better. Our percentage of maternal deaths due to toxemia is still high, but hemorrhage ranks first. We handle the third stage of labor in a fairly routine manner. Most of the placentas were delivered within 10 minutes. After 15 minutes extraction is usually performed. With regard to Dr. McElin’s comments, the 41 patients with blood losses of over 500 C.C.
Postpartum
hemorrhage
717
were actually among the multiparous group. We attempted to compare these with the remainder of the multiparous group in order to arrive at some differences in the method of delivery, etc. In regard to routine practice in the department, we tried, in this series, to encourage spontaneous delivery and the number of forceps deliveries was very low. Part of the blood loss in the primiparas was undoubtedly due to episiotomy and this was probably increased when repair was performed by the house staff, as was pointed out by Dr. Calkins many years ago. The estimated blood loss for episiotomy in a group of these patients was approximately 150 C.C. Definite figures for blood loss due to perineal or cervical lacerations could not be determined. With regard to the dose of sparteine sulfate and the oxytocic agents chosen, these were empirical and depended upon a number of extraneous factors. I might add, however, that in the last few months we have been using 75 mg. of sparteine sulfate in the same manner and, while we have not conducted precise blood loss studies on these patients, we have been determining how many patients required additional oxytocics. The number was less in the sparteine than in a comparable control group, but not significantly so. This suggests that 75 mg. of sparteine sulfate may be too low a dose. With regard to Dr. Briscoe’s comments about sparteine sulfate, we have the same reservations about its use during labor. We found tetanic uterine contractions to be common in a series of 50 cases and we have discontinued the use of sparteine before delivery. We do think that it has, and possibly will continue to have, some value as a postpartum oxytocic.
hemorrhage
NEWTON,
M.D.
Missis&@&
T H E A M o u N T of blood lost during and immediately after delivery remains an important clinical problem for three reasons. First, severe bleeding may occur suddenly and unexpectedly and transform a normal delivery into a catastrophe. Moreover, hemorrhage is still a leading cause of maternal death. For example, in Mississippi, during the years 1959 through 1963, 72 of 252 (29 per cent) maternal deaths studied by the State Medical Association’s Committee on Maternal and Child Care were found to be due to hemorrhage (Table I). Second, moderate amounts of blood lost during delivery may complicate the puerperium and debilitate the mother so that she is not in optimum condition for the stress of caring for her newborn baby, as well as her husband and other children. Third, there is still need for finding new, safe, and effective ways of preventing and treating obstetrical hemorrhage. Transfusions, ergot derivatives, and oxytocin have, indeed, saved many lives, but all have some disadvantages. This report covers a series of investigations in the field of obstetrical blood loss. First, we spent some time developing and determining the accuracy of our method of measurement. Second, we studied blood loss in a group of normal patients who received no oxytocics unless excessive bleeding occurred. From the Defiartment Gynecology, University School of Medicine.
of
Obstetrics
Finally, we tested the effect of synthetic oxytocin and sparteine sulfate on measured blood loss. Methods
of
measurement
The acid hematin spectrophotometric method was chosen for determining blood loss. Briefly, this involves the collection of liquid material and pads, sponges, etc., containing blood in a solution of O.lN hydrochloric acid. By this means, the hemoglobin is converted into acid hematin. Appropriately diluted samples of this fluid and of the patient’s blood drawn at the same time are then read in the Klett-Summerson colorimeter. Blood loss can then be calculated by a simple formula.l~ * The accuracy of the method was tested by a series of in vitro experiments. Under conditions simulating delivery, it was possible to recover an average of 97.9 per cent of the blood used when citrate had been added and 88.5 per cent when the blood was fresh. Using perineal pads to simulate postpartum conditions it was possible to recover an average of 92.9 per cent of the blood used. It is of interest that a similarly high degree of accuracy has recently been reported by Miller.3 The value of accurate measurement of blood loss compared with the usual practice of estimation became apparent as the study
and
of Mississippi
Table I. Maternal
These studies were supported in part by grants from Sandoz Pharmaceuticals, Division of Sandoz, Incorporated, Hanover, New Jersey, and from Ayerst Laboratories, New York, New York.
Maternal Year
Presented by invitation at the Seventy-sixth Annual Meeting of the American Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Sept. 9-11, 1965.
711
1
Total
deaths deaths 1
from due No.
hemorrhage to hemorrhage )
%
1959 1960
52 58
19 14
37 24
1962 1961 1963
53 48 41
14 10 15
;ii 37
712
March 1, 1966 Am. J. Obst. L Gynec.
Newton
proceeded. Thus, in 100 patients the mean error of estimation as compared with measurement was 46 per cent, even allowing for the fact that those making the estimation had been sensitized by the conduct of the investigation. More importantly, estimations tended to be low when the blood loss was high-20 per cent low when the loss was between 400 and 499 C.C. and 34 per cent low when the loss was 500 C.C. or more. Control patients. One hundred and five patients were studied. Twenty-eight were primiparas and 77 were multiparas. They were included only if they were at 36 weeks of gestation or more, had had no serious complications of pregnancy, and were expected to have no serious difficulties during labor and delivery. During the period of study, all patients who met the criteria were included, unless the labor was so rapid or the delivery suite so busy that it was impossible to collect the samples accurately. Patients were managed during labor and delivery according to the usual practices of the department. No oxytocics were given these patients unless, in the opinion of the resident in charge of the delivery suite, bleeding was sufficient to require treatment. In this case, synthetic oxytocin, 20 units in
Table II. Obstetrical
blood
1,000 cc. 5 per cent dextrose in water. was given intravenously. In each patient, blood loss was measured for three periods (1) while she was on the delivery table (on-table loss), (2) for the first hour after she was removed from the delivery table and while she was still in the delivery suite (post-table loss), and (3) during the remainder of the first 24 hours post partum (1 to 24 hour loss). Large individual variations in blood loss were apparent among the normal patients (Table II). As an example, the on-table loss in multiparas showed a very large standard deviation and a wide range. Further analysis of these variations resulted in some interesting observations. The large majority of the losses were below 300 C.C. (in 49 of 77, 64 per cent). Only 4 were between 300 C.C. and 400 C.C. and 7 between 400 C.C. and 500 cc., while 17 patients (22 per cent) had losses of over 500 c.c., a figure which is normally considered an obstetrical hemorrhage. The same trend was noted in the post-table loss in multiparas. Sixty-three patients (82 per cent) lost under 100 cc., one lost between 100 C.C. and 149 c.c., 3 lost between 149 C.C. and 200 cc., and 10 lost over 200 C.C. At the one to 24 hour period this tendency for certain women to have excessive losses was much less marked. Here 66 of 73 multiparas (90 per cent) lost less than 100 cc. Only 3 lost more than 200 C.C. The on-table loss appeared to be considerably higher in primiparas than in multiparas but this difference was not statistically significant owing to the wide individual variations and the small numbers of patients, However, primiparas lost significantly less blood than multiparas in the post-table and
loss in normal
women Primiparas
Multiparas
No.~bl+%JL On-table Post-table 1 to 24 hours
28 28 27
No.~bl;.~
625+337 20+ 17 462 56
77 77 73
3142310 93 2 155 87 + 139
post partum
Table III. Effect of synthetic
oxytocin
on blood
loss
Primiparas
Multiparas
Control
On-table Post-table 1 to 24 hour
post partum
Oxytocin
No.
Mean blood loss (CL.)
28 28 27
625 20 46
No. 13 13 7
Control
Mean blood loss (C.C.) 401 19 28
No. :: 73
Oxytocin
Mean blood loss (Cd.)
No.
Mean blood loss (C.C.)
314 93 87
37 37 26
325 43 142
Volume Number
94 5
Postpartum
in the 1 to 24 hour periods (p = lessthan 0.01 in both cases). In the post-table period this may have been due to the fact that more primiparas had received intravenous oxytocin to control excessive bleeding. Effect of synthetic oxytocin on blood loss. Fifty patients, 13 primiparas and 37 multiparas, received synthetic oxytocin, 10 units intramuscularly, after the delivery of the placenta and 10 units intramuscularly every 6 hours thereafter. They were selected by the same criteria as the control patients and were alternated with them. Thy received the same type of obstetrical management. No significant differences in blood loss at any of the three periods studied were noted between the patients receiving synthetic oxytocin and the controls (Table III). However, the beneficial effect of synthetic oxytocin upon blood losswas more clearly shown by the smaller number of patients requiring additional oxytocics to control excessive bleeding immediately after delivery (Table IV). These differences were highly significant statistically for both primiparas and multiparas (p = lessthan 0.01). Effect of sparteine sulfate on blood loss. Forty-eight patients (11 primiparas and 37 multiparas) received sparteine sulfate 150 mg. intramuscularly after the delivery of the
16 13
12 0
58 36
713
baby’s anterior shoulder and 150 mg. intramuscularly every 4 hours thereafter. They were chosen for inclusion in the study by the same criteria used for the control patients and were randomly selected for the administration of sparteine sulfate. No significant differences in blood loss were noted between the patients receiving sparteine sulfate and the controls (Table V). However, sparteine sulfate was also shown to be an effective oxytocic agent by the fact that a smaller number of the patients receiving it required additional oxytocics to control hemorrhage (Table VI) . Again these differences were highly significant statistically for both primiparas and multiparas (p = lessthan 0.01). Comment
In these studies the mean total loss of blood during and shortly after delivery (ontable and post-table losses) was 470 cc. Allowing for a measurement error of 10 per cent and for 60 C.C. contained in the average placenta,4 a total blood loss of 577 C.C.is obtained. This figure agreesfairly well with that determined by Pritchard5 using chromium-labeled red cells. However, the actual loss by the average woman was probably more than this, since excessiveloss was controlled by giving additional oxytocics. Our data do not provide any explanation for the marked individual differences in blood loss. All the patients studied were supposedly normal although variations in general health or nutritional status might have been present. Furthermore, review of the 41 multiparas who lost a total of more than 500 C.C.blood during the on-table and post-table periods combined showed that
Table IV. Additional oxytocics in patients receiving synthetic oxytocin
No oxytocic Synthdtic oxytocin
hemorrhage
19 1
Table V. Effect of sparteine sulfate on blood loss Primiparas
Multiparas
Control
No. On-table Post-table 1 to 24 hour
postpartum
28 28 27
Sparteine
Mean blood loss (c.c.) 625 20 46
No. 11 11 11
Sfiarteine
Control
Mean blood loss (c.c.) 599 46 69
No. 77 77 73
Mean blood loss (c.c.) 314 93 87
No. 37 37 36
Mean blood loss (CL.) 300 61 99
714
March 1, 1966 Am. J. Obst. & Gynec.
Newton
Table
VI. Additional
receiving
sparteine
oxytocics sulfate Additional
Patients receiving delivery
Primijmras at
Not given
No oxytocic Sparteine sulfate
16 10
I Given 12 1
in patients
oxytocics Multiparas Not I given 58 35
I Given 19 2
there were no differences between them and the remainder as far as age, parity, length of labor, analgesia, anesthesia, method of delivery, or trauma at delivery were concerned. Of the two oxytocic agents used, synthetic oxytocin needs little discussion. It has been established as a satisfactory drug whose main disadvantage is that it takes several minutes to act if given intramuscularly. Sparteine Its sulfate deserves additional comment. main reported use has been to stimulate labor but it has not been used much post partum. Our experience indicates that it is an effective oxytocic agent when used in this manner. No untoward side reactions and specifically no retained placentas were noted. Hypertension was not found, although the mean blood pressure of the control group fell a little more postpartally than that of the group receiving sparteine. Summary
and
conclusions
1. Blood loss was measured during delivery, in the first hour after removal from
the delivery table and in the remainder of the first 24 hours post partum in 203 obstetrical patients by the acid hematin spectrophotometric method. 2. In 105 normal patients who received no oxytocics unless bleeding was excessive the mean total on-table and post-table loss was 470 cc. During the rest of the first 24 hours after delivery the mean loss was 76 cc. Multigravidas lost significantly more blood than primigravidas during the posttable and 1 to 24 hour periods. Wide individual variations in blood loss were noted. No consistent cause for this could be found. 3. Blood loss was measured in 50 normal patients who were given 10 units of synthetic oxytocin intramuscularly after the delivery of the placenta and in 48 patients who were given 150 mg. sparteine sulfate at the delivery of the baby’s anterior shoulder. There were no significant differences between either of these two groups of patients and the controls in measured blood loss in any of the three periods studied. 4. Both synthetic oxytocin and sparteine sulfate were found in this study to be effective oxytocic agents in that a significantly smaller number of patients in each treated series than of those in the control series required additional oxytocics for the management of hemorrhage. 5. No special advantage was found for continuing the use of oxytocics routinely in the puerperium unless they were indicated by excessive bleeding
REFERENCES
1.
2. 3.
Newton, M., Mosey, L. M., Egli, G. E., Gifford, W. B., and Hull, C. T.: Obst. & Gynec. 17: 9, 1961. Newton, M., and Bradford, W. M.: Obst. & Gynec. 17: 229, 1961. Miller, R. L.: Obst. & Gynec. 25: 553, 1965.
4. 5.
Newton, M., and Moody, Gynec. 18: 305, 1961. Pritchard, J. A., Baldwin, C., and Wiggins, K. M.: GYNEC. 84: 1271, 1962.
A.
R.:
Obst.
&
R. M., Dickey, AM. J. OBST.
J. &
Discussion DR. W. NORMAN THORNTON, JR., Charlottesville, Virginia. Hemorrhage as a leading cause of maternal death is truly a tragedy in modem obstetrics. It will remain one of the leading causes of maternal death until State Health
Departments to maintain
stetrical
require adequate
rural maternity hospitals supplies of blood for ob-
emergencies.
now must depend 50 miles away.
Some of these small units on
blood
banks
some
30
to
Volume !?4 Number 5
This is the fourth report by Dr. Newton and his associates which clearly indicates that the blood loss associated with delivery and the immediate puerperium is significant and much greater than the inaccurate estimates which we usually employ. The mean total loss, including that contained in the placenta, of 577 ml. is a significant amount and may well account for some of the anemias so commonly seen in the grand multipara who frequently enjoys only a few months between pregnancies. Dr. Newton’s measured loss is in agreement with that reported by Pritchard and the accuracy of the method has recently been confirmed by Miller. The author states that he is unable to explain the marked individual variations in blood loss, since in his series, there were no significant differences in measurable factors. One wonders if a more meticulous assessment of the vagina, cervix, and uterus might not have given some answer to these individual variations in blood loss. Recently, we have had the opportunity to review the findings in 1,000 consecutive explorations of the uterus, cervix, and vagina immediately following delivery of the placenta. In spontaneous deliveries, unsuspected cervical lacerations were found in 4.73 per cent and vaginal lacerations in 4.1 per cent of the patients. In forceps deliveries, cervical lacerations were SUStained in 13.3 per cent and vaginal lacerations in 14.9 per cent of the patients. In addition to these sources of blood loss, placental fragments were found in 1 per cent of the uteri explored. Dr. Newton’s clinical observation that sparteine sulfate is an effective oxytocic agent confirms some observations made in our laboratories. In vitro assessment of isolated human myometrial strips excised from gravid uteri show that increasing concentrations of sparteine sulfate result in a progressive increase in frequency of contractions as well as tone associated with a progressive decrease in contractile waves. The more striking observation and one which may be associated with a reduction in blood loss was noted in the contractile response of strips of human uterine artery on exposure to sparteine sulfate. This resulted in a marked increase in tone and frequency of contractions whereas oxytocin produced no appreciable change in contractile response. Additional in vitro observations indicate that the action of sparteine sulfate on isolated human uterine artery strips is similar to that of ergonovine maleate. The author is to be congratulated for presenting information which indicates that both spar-
Postpartum
hemorrhage
715
teine sulfate and synthetic oxytocin are effective uterine stimulants, and that a significantly smaller number of patients receiving either of these agents required additional oxytocics for the control of hemorrhage. DR. FRANK E. WHITACRE, Nashville, Tennessee. Dr. Newton’s figures on maternal deaths in the State of Mississippi were interesting. In Tennessee during the same period of time, 1959 through 1963, we had 407,323 births. There were 190 maternal deaths and of these 44 or 23.1 per cent were due to hemorrhage. Fifty or 26.3 per cent were due to toxemia of pregnancy and 40 or 21.1 per cent were due to infection. It is commonly said that these three major causes of maternal deaths are preventable, but perhaps many of you would agree with me that this is not always the case. Dr. Newton’s method of measuring blood loss is certainly an improvement over inaccurate estimation. In the group of normal patients who received no oxytocics unless bleeding was excessive, the total blood loss of 470 C.C.is higher than I would expect. The numerous causes of postpartum bleeding have been analyzed many times. We feel, however, that two of the causes are sometimes ignored. First, unwise conduct of the third stage which usually means giving the placenta insufficient time to separate and ignoring the principle to never press on a relaxed uterus. The second common cause is a foreign body in the uterus and an ordinary blood clot is much more frequent than retained secundines. Although the intravenous drip using dilute oxytocin was at first used as a method of induction, and/or stimulation of labor, the method is also most useful in controlling the bleeding of patients with incomplete abortion and bleeding in the postpartum period. I would expect it to be superior to the use of sparteine sulfate because after intramuscular injection, a drug is not as immediately effective as by intravenous injection and its action cannot be controlled as well. I would like to call attention to the effect of bleeding in late pregnancy on the baby. An estimation would indicate that at 28 weeks the fetus has about 85 C.C. of blood and weighs about 2 pounds, 4 ounces. The amount of blood and the body weight will be approximately tripled by the thirty-ninth week; therefore, any given amount of blood lost by the fetus at 28 weeks is three times as great as at term. Under the direction of Dr. Everett Clayton at the Nashville Metropolitan General Hospital,
716
Newton
we perfected a method of identification of fetal erythrocytes in the maternal circulation and then on the suggestion of Dr. Edith Potter, we have been determining the amount of fetal blood loss in third trimester vaginal bleeding. This work will appear in the literature in the near future. DR. T. W. MCELIN, Evanston, Illinois. The relatively unchanging percentage of maternal deaths due to hemorrhage emphasize the need for continued vigorous research and more intensive patient care. Evidence for this is Dr. Newton’s Table I showing that 37 per cent of all maternal deaths in Mississippi in 1959 were due to hemorrhage, and that the figure in 1963 was again 37 per cent. My remarks will be directed to four points: 1. General agreement is to be anticipated with two of Dr. Newton’s conclusions: (A) The greater accuracy of measurement of blood loss compared with estimation is apparent; and (B) There is no special advantage in the routine usage of oxytocics in the postpartum period. 2. I would appreciate further information regarding the definition of “normal patients.” I about the “usual” am, of course, wondering variables of delivery: spontaneous versus operative delivery, the type of episiotomy, presence or absence of lacerations, the performance or nonperformance of uterine exploration, etc. We are told only that comparisons of this type were made in 41 patients who had a blood loss in excess of 500 cc. This information looms important as we have already been asked to analyze variables, for example, of the order of 314 + 310 cc. measured blood loss in one instance or 93 + 155 cc. in another instance. 3. 1 was interested in the author’s selection of routine dosages of synthetic oxytocin and sparteine sulfate given at the time of delivery in his study of measured blood loss in two separate groups of patients. Ten units of intramuscular synthetic oxytocin was administered after delivery of the placenta to one group-a dosage over 20 times that which might be given as an intramuscular oxytocic dosage during labor. Contrariwise, 150 mg. of sparteine sulfate was administered after delivery of the anterior shoulder to a comparable group. This is, of course, a recommended dosage of this drug for oxytocic purposes in labor. The conclusion is then presented, “there were no significant differences between either of these two groups of patients and the controls in measured blood loss.” A vastly greater amount of oxytocin as compared to sparteine sulfate, relative to the usual ante-
March 1, 1966 Am. J. Obst. % Gynec.
partum dose, was given and, hence, I question the validity of this particular conclusion. 4. Comment should be made on the conclusion that there is no difference in the postpartum blood loss of those patients given oxytocin and sparteine sulfate at the time of delivery. If indeed this is so, I should like to record my preference for oxytocin. Despite my significant enthusiasm for sparteine sulfate as an oxytocic agent, based on our extensive and published experience from Evanston Hospital, I must acknowledge that the intramuscular administration of certain dosage forms of sparteine sulfate is often moderately and, occasionally, severely uncomfortable for the patient. DR. CLARENCE BRISCOE, Philadelphia, Pennsylvania. Dr. Newton has correctly emphasized the impact of blood loss on maternal mortality and debility. The attack on the problem should begin with the antenatal administration of iron. Unfortunately, high hemoglobin levels do not guarantee adequate iron reserves; hence, iron administration should be routine, not only during pregnancy but following it as well. It was surprising that little difference was noted between oxytocin and sparteine sulfate. My romance with sparteine was early and disenchanting. It is an unpredictable drug, producing tetanic contractions in one uterus or none at all in another. Using a Pastore collecting tray to measure blood loss, we have found distinct advantage in the intravenous injection of ergot at the birth of the shoulders. Trapped placentas, increasing the incidence of manual removal, is a complication of this method. Without this prophylactic dose, the uterus, often flabby, could be made to contract by direct intrauterine injection of ergonovine, either transabdominally or transvaginally through the anterior fornix. Some of our students may practice in conmmunity hospitals without house or nursing staff available for venipuncture and they should be aware of this technique. By packing the upper vagina, blood loss during slow intern episiotomy repairs was measured and found to average 100 ml., reaching 500 ml. in one instance. Since 1948, I have practiced planned deliberate exploration of each postpartum uterus. Retained secundines were found in 4 per cent of our cases. Uterine anomalies, submucous myomas, thin scars, clots and accessory placental lobes are occasionally uncovered. An atonic uterus is immediately discovered and massaged.
Volume 94 Number 5
Blood loss is decreased and febrile morbidity is lower while postpartum hemoglobin levels are higher than in the unexplored cases. DR. NEWTON (Closing). In reply to Dr. Thornton, we have looked at the figures for maternal deaths due to hemorrhage in Mississippi. By 1961 a steady decrease had become apparent, possibly due to the fact that the blood bank situation in the state had improved. In 1963, however, deaths from hemorrhage again increased and we were somewhat discouraged. We have not routinely explored the uterus, as suggested by Drs. Thornton and Briscoe, and, therefore, cannot make any statements about this. I am interested in the arterial tone studies with sparteine sulfate, mentioned by Dr. Thomton. We have been concerned lest sparteine sulfate produce an elevation of blood pressure in some patients such as occurs occasionally with ergot derivatives. We have not been able to prove that this happens. In none of the patients given sparteine sulfate was there any startling rise in blood pressure, but, the overall fall in blood pressure post partum, based on means, was somewhat less than in the control group. With regard to the percentage of maternal deaths due to hemorrhage, it is evident, in reply to Dr. Whitacre, that in Tennessee blood banks are better. Our percentage of maternal deaths due to toxemia is still high, but hemorrhage ranks first. We handle the third stage of labor in a fairly routine manner. Most of the placentas were delivered within 10 minutes. After 15 minutes extraction is usually performed. With regard to Dr. McElin’s comments, the 41 patients with blood losses of over 500 C.C.
Postpartum
hemorrhage
717
were actually among the multiparous group. We attempted to compare these with the remainder of the multiparous group in order to arrive at some differences in the method of delivery, etc. In regard to routine practice in the department, we tried, in this series, to encourage spontaneous delivery and the number of forceps deliveries was very low. Part of the blood loss in the primiparas was undoubtedly due to episiotomy and this was probably increased when repair was performed by the house staff, as was pointed out by Dr. Calkins many years ago. The estimated blood loss for episiotomy in a group of these patients was approximately 150 C.C. Definite figures for blood loss due to perineal or cervical lacerations could not be determined. With regard to the dose of sparteine sulfate and the oxytocic agents chosen, these were empirical and depended upon a number of extraneous factors. I might add, however, that in the last few months we have been using 75 mg. of sparteine sulfate in the same manner and, while we have not conducted precise blood loss studies on these patients, we have been determining how many patients required additional oxytocics. The number was less in the sparteine than in a comparable control group, but not significantly so. This suggests that 75 mg. of sparteine sulfate may be too low a dose. With regard to Dr. Briscoe’s comments about sparteine sulfate, we have the same reservations about its use during labor. We found tetanic uterine contractions to be common in a series of 50 cases and we have discontinued the use of sparteine before delivery. We do think that it has, and possibly will continue to have, some value as a postpartum oxytocic.