Maternal floor infarction
Volume 167 Number 5
17.
18. 19. 20.
21.
Major basic protein as a predictor of preterm labor: a preliminary report. AM J OBSTET GYNECOL 1987;156: 790-6. Filley WV, Holley KE, Kephart GM, Gleich GJ. Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma. Lancet 1982;2:11-6. Peters MS, Schroeter AL, Kephart GM, Gleich GJ. Localization of eosinophil granule major basic protein in chronic urticaria. J Invest Derm 1983;81 :39-43. Krenik KD, Kephart GM, Offord KP, Dunnette SL, Gleich GJ. Comparison of antifading agents used in immunofluorescence. J Immunol Methods 1989; 117:91-7. Wassom DL, Loegering DA, Solley GO, et al. Elevated serum levels of the eosinophil granule major basic protein in patients with eosinophilia. J Clin Invest 1981:67:65161. McConahey PJ, Dixon FJ. A method of trace iodination
22.
23. 24. 25.
of proteins for immunologic studies. Int Arch Allergy Appl Immunol 1966;29:185-9. Nelson DM, Crouch EC, Curran EM, Farmer DR. Trophoblast interaction with fibrin matrix: epithelialization of peri villous fibrin deposits as a mechanism for villous repair in the human placenta. AmJ Patho11990; 136:85565. Davies BR, Casanueva E, Arroyo P. Placentas of smallfor-dates infants: a small controlled series from Mexico City, Mexico. AMJ OBSTET GY:--IECOL 1984;149:731-6. Altshuler G, Russell P, Ermocilla R. The placental pathology of small-for-gestational age infants. A~ J OBSTET GYNECOL 1975;121:351-9. De Lia JE. Placenta and fetal development. In: Scott JR, DiSaia PJ, Hammond CB, Spellacy WN, eds. Danforth's obstetrics and gynecology. Philadelphia: JB Lippincott. 1990: 101.
The effect of placental management at cesarean delivery on operative blood loss Charles M. McCurdy, Jr., MD, Everett F. Magann, MD, Cynthia J. McCurdy, MD, and Andrew K. Saltzman, MD Camp Lejeune, North Carolina OBJECTIVES: The effect of alternative methods of placental delivery at cesarean section on blood loss has not been reported. The hypothesis of this study was that spontaneous expUlsion of the placenta would reduce operative blood loss, compared with that of manual extraction during cesarean delivery. STUDY DESIGN: We prospectively randomized and compared outcomes of 62 gravid women with manual (n = 31) or spontaneous (n = 31) placental delivery at cesarean section. Operative blood loss was measured directly. RESULTS: Blood loss measured at cesarean delivery was greater in the manually delivered group (967 ± 248 ml) than in the spontaneously delivered group (666 ± 271 ml, p < 0.0001). The incidence of postpartum endometritis was sevenfold greater in the manual than the spontaneous group (23% vs 3%, respectively; p < 0.05). CONCLUSIONS: We conclude that spontaneous expUlsion of the placenta at cesarean delivery results in less operative blood loss and a lower incidence of postoperative endometritis. (AM J OBSTET GYNECOL 1992;167:1363-7.)
Key words: Cesarean delivery, placenta, blood loss Cesarean delivery is one of the most commonly performed major operations in the United States. Patients undergoing abdominal delivery are exposed not only From the Department of Obstetrics and Gynecology, Naval Hospital Camp Lejeune. This article represents the findings of the authors and is not necessarily the opinions of the United States Government. Received for publication November 18, 1991; revised March 18, 1992; accepted March 31,1992. Reprint requests: Charles M. McCurdy, Jr., MD, Department of Obstetrics and Gynecology, University of Arizona, Health Sciences Center, 1501 Campbell Ave., Tucson, AZ 85724.
6/1138211
to risks inherent to major abdominal surgery but to additional risks (e.g., thromboembolic phenomena, aspiration pneumonia) in association with physiologic alterations of pregnancy. At term the gravid uterus is perfused at a rate of 500 to 750 mllmin.! This physiologic hyperperfusion results in an average blood loss at cesarean deE very of approximately 1000 ml and a risk for operative hemorrhage." Infectious morbidity is estimated at 5% to 85% in postcesarean patients." Studies of the possible role the technique of placental delivery might play in operative blood loss at cesarean delivery have not been reported. In texts of operative
1364
McCurdy et al.
obstetrics that address placental delivery, a manual shearing of the placenta from its attachment at the decidua basalis after delivery of the fetus is suggested. Spontaneous expulsion of the placenta is not discouraged unless occurring in an untimely fashion!' 5 We prospectively examined the effect of placental management on operative blood loss at cesarean delivery. We hypothesized that spontaneous delivery of the placenta, similar to that during vaginal deliveries, would reduce blood loss and would not be associated with a significantly prolonged duration of surgery. Methods
This prospective study was performed in 62 women undergoing cesarean delivery at Naval Hospital Camp Lejeune between September 1990 and March 1991. Regional and institutional research review board approval was obtained for the study, as was written informed consent from all volunteers. Sixty-two patients who were candidates for cesarean delivery were preoperatively enrolled consecutively and assigned randomly to study or control groups by randomized cards in numerically ordered and sealed envelopes. The study group was that group of patients having spontaneous expulsion of the placenta at cesarean delivery. The control group consisted of those patients with manual detachment of the placenta at cesarean delivery. Patients 15,000/ml), and at least two temperature elevations (~38° C) >6 hours apart) after the first 24 hours post partum. Data on all 62 patients enrolled were available for review with no postenrollment exclusions from this study. Statistical analysis of continuous data was by the two-tailed Student t test. Discrete data were analyzed via analysis of variance. Statistical significance was set for values of p < 0.05. Results
Demographic characteristics of all patients are compared in Table I. Parity and ethnicity were not significantly different in this study. There was no significant differences between the two groups for antenatal complications of hypertension, postdatism, diabetes, bleeding disorders, obesity, fetal growth disorders, and antenatal assessment outcomes. Indications for cesarean delivery included: arrest of labor (50%), fetal malpresentation (18%), fetal distress (6%), active genital herpes (5%), and elective repeat cesarean delivery (21 %). No differences existed between the groups for indications for cesarean delivery. Other preoperative comparisons are reported in Table II. In addition to oxytocin, four patients had been treated with terbutaline, three with prostaglandin E2 gel, and five received magnesium sulfate with no statistically significant differences between the groups. Amniotic fluid index determined preoperatively did not vary significantly. Labor occurred in 18 of 31 and 20 of 31 patients in the study and control groups, respectively (not significant). Rupture of the membranes was documented in 14 of 31 patients having spontaneous expulsion and 18 of31 patients undergoing manual extraction of the placenta (not significant).
Placental management methods at cesarean delivery
Volume 167 Number 5
Table I. Patient demographics
Table III. Operative data Placental delivery
spontaneous (N = 31)
Age (yr) Gravidity Gestational age (wk) Weight (kg) Admission hemoglobin (gm/dl)
24.2 1.9 38.6 81.2 12.5
5.5 1.0 2.4 ± 6.8 ± 1.0 ±
± ±
Placental delivery
Manual (N = 31)
24.5 1.8 39.6 79.5 12.0
4.0 1.0 ± 1.4 ± 5.1 ± 2.5 ±
±
Data are presented as mean ± SD. p, Not significant.
Table II. Preoperative data Placental delivery
Presence of labor (No.) Oxytocin use (No.) Primary cesarean delivery (No.) Amniotic fluid index (cm)
1365
Spontaneous (N = 31)
Manual (N = 31)
18 (58%)
20 (65%)
13 (42%) 21 (68%)
14 (45%) 25 (81 %)
10.5 ± 3.9
Spontaneous (N = 31)
Duration of surgery (min) Uterine incision "open" (min) Duration of stage III (min) Measured blood loss (ml) Estimated blood loss (ml)
The incidence of regional anesthesia was not significantly different (25/31 [81 %] in the spontaneous group and 23/31 [74%] in the manual placental delivery group). Antibiotic prophylaxis for obstetric and medical indications was given in 22 of 31 (71 %) and 24 of 31 (77%) for the spontaneous and manual groups, respectively (not significant). Abdominal incisions were transverse in 29 of 31 and 30 of 31 patients in the spontaneous and manual groups, respectively. Additionally, transverse uterine incisions were performed in 30 of 31 and all of the 31 patients in the two respective groups (not significant). Comparative operative data are listed in Table III. Tubal ligation was performed in an equal number of patients in the study and control groups (n = 5 in each). Again, uterine incision "open" refers to length of time recorded from initiation of uterine incision to completion of imbricating layer. Measured blood loss was significantly greater in the manually detached placenta group than in the spontaneously delivered placenta group (p < 0.0001). Estimated blood loss was greater in the manually detached group than in the spontaneously delivered group (p < 0.05). Surgical complications were sporadic and included: uterine atony (n = 1), uterine incisional extension (n = 1), and aspiration pneumonia (n = 1). There was no difference between the study groups regarding the incidence of surgical complications. Postoperative data including decrease in hemoglobin
32.7 ± 6.3
35.1 ± 8.4
13.0 ± 3.7
12.9
±
3.4
2.0 ± 0.9
1.6 ± 0.9
666 ± 271*
967 ± 248
764 ± 228t
924 ± 304
*p < 0.0001, compared with control. tp < 0.05, compared with control.
Table IV. Postoperative data Placental delivery
10.3 ± 3.7
p, Not significant.
Manual (control) (N = 31)
Decrease in hemoglobin (gm/dl) 12 hr after operation 48 hr after operation Postoperative hospital stay (days) Incidence of endometritis (No.) Incidence of other complications (No.)
Spontaneous (N = 31)
Manual (control) (N = 31)
1.2 ± 0.9 1.4 ± 0.8* 3.9 ± 1.1*
1.5 ± 0.9 1.9 ± 0.8 4.8 ± 2.1
1 (3%)*
7 (23%)
3 (10%)
2 (6%)
*p < 0.05, compared with controls. at 12 and 48 hours are reported in Table IV. No significant difference existed at 12 hours; however, the decrease in postoperative hemoglobin was significantly greater in the group with manual removal than in the spontaneous expulsion group at 48 hours. In addition, the incidence of puerperal endometritis was sevenfold higher in the manual group. Postoperative hospital stay was also significantly longer in the group undergoing manual placental delivery. The incidence of other complications including wound infection (n = 2), urinary tract infection (n = 2), and transfusion (n = 1) was not statistically different in the two groups.
Comment In this study a significant decrease in measured blood loss was seen in patients undergoing cesarean delivery in whom the placenta was spontaneously, rather than manually, removed. Additional support for greater blood loss in the manual placental delivery group was found with a significantly greater decrease in hemoglobin concentration at 48 hours after operation (1.9
1366 McCurdy et al.
vs 1.4 gm/dl). The duration of surgery, duration of operative stage III, and length of time the uterine incision was open were not altered by the mode of placental delivery. Measured blood loss at delivery, vaginal or cesarean, has been compared by hemodilutional spectrophotometric assays and radiochromium-labeled red blood cell assays.2. 7-9 In this study blood loss was measured by volume and gravimetric assessment. A few alterations in our technique deserve attention. Initially, the use of the 10 Ban-drape laparotomy drape must be considered. This recent innovation in the management of excess body fluids at abdominal surgery allows as well for the more thorough collection of all fluids not absorbed by laparotomy packs. Measurement of collected fluid, dry and wet pack weight, and all irrigation fluids should then give an accurate estimate of the true operative blood loss. The second problem encountered in measuring blood loss at delivery is the confounding factor of an undetermined volume of amniotic fluid. Preoperative amniotic fluid index assessment was used to correct for amniotic fluid volumes. Although amniotic fluid index is a semiquantitative method of assessing amniotic fluid volume, the absence of a significant difference between the mean amniotic fluid index values of the study groups suggests that the volumes of amniotic fluid collected at cesarean delivery were similar in the two groups. This amniotic fluid volume may lead to an overestimation of measured blood loss. After vaginal delivery endogenous oxytocin is released, myometrial cells shorten, and the placental implantation site involutes. This process also occludes vessellumina, thus diminishing blood flow to the decidua basalis. Placental cleavage occurs when a relatively fixed placental surface area is implanted over an involuting site. A retroplacental hematoma forms and is confined by the remaining placental attachments; this results in a hydrostatic effect on acute blood loss at the implantation bed. Vasospasm and local involvement of the coagulation cascade also lead to hemostasis. This is clinically evident after vaginal birth by the palpation of a firm, involuted uterine fundus at about the level of the umbilicus. At cesarean birth the tendency of the uterus to undergo similar changes may be appreciated both visibly and by palpation, before actual delivery of the placenta. Manual shearing of the placenta from the decidua basalis before significant involution of the implantation bed theoretically would result in unaltered perfusion to this area and increased blood loss. A qualitative disadvantage to manual placental extraction was proposed by Queenan and Nakamoto,IO who noted an increased rate of rhesus factor isoimmunization after this method of placental delivery. In the current study an increased rate of postoperative uterine infection followed manual placental delivery
November 1992 Am J Obstet Gynecol
(23% vs 3%). The relatively high incidence of endometritis after manual extraction noted in this study is in concordance with recent published trends of the incidence of postcesarean endometritis ranging from 20% to 38% and the range of postoperative infectious morbidity existing in the literature." 12 Military studies have typically demonstrated a lower incidence of this entity, consistent with the overall incidence of 13% noted in this study. 13. 14 Tissue trauma, maternal autotransfusion of bacterially contaminated blood before implantation site involution, surgical contamination, and excessive blood loss are possible explanations for this finding. This concomitant increased postoperative hospital stay in patients undergoing manual placental extraction was related to the increased incidence of endometritis and subsequent duration of antibiotic therapy. Although not demonstrated in this study, spontaneous delivery of the placenta may be of benefit in cases of pathologic placental implantation (e.g., placenta accreta, lower uterine segment placental implantation) where maximal decrease in implantation bed surface area and spiral artery perfusion pressure would be desirable. In conclusion, spontaneous expulsion of the placenta at cesarean delivery was associated with decreases in surgical blood loss as measured and assessed by change in hemoglobin concentrations. Incidence of postoperative endometritis and consequent prolonged hospital stay were also reduced in women in whom this surgical technique was used.
REFERENCES I. Assali NS, Douglas RA, Baird WW. Measurement of uterine blood flow and uterine metabolism. AM] OB8TET GyNECOL 1953;66:248-53. 2. Pritchard ]A, Baldwin RM, Dickey ]C, Wiggins KM. Blood volume changes in pregnancy and the puerperium. II. Red cell loss and changes in apparent blood volume during and following vaginal delivery, cesarean section, and cesarean section plus total hysterectomy. AM] OB8TET GYNECOL 1962;84:1271-82. 3. Duff P. Pathophysiology and management of postcesarean endomyometritis. Obstet Gynecol 1986;67:269-75. 4. Phelan ]P, Clark SL. Cesarean delivery: the transperitoneal approach. In: Phelan ]P, Clark SL, eds. Cesarean delivery. New York: Elsevier, 1988:201-18. 5. Hibbard LT. Cesarean section and other surgical procedures. In: Gabbe SG, Niebyl ]R, Simpson ]L, eds. Obstetrics: normal and problem pregnancies. New York: Churchill Livingstone, 1986:517-48. 6. Phelan]P, Smith CV, Broussard P, Small M. Amniotic fluid volume assessment with the four-quadrant technique at 36-42 weeks' gestation.] Reprod Med 1987;32:540-2. 7. Wilcox FC, Hunt AB, Owen CA. The measurement of blood lost during cesarean section. AM] OB8TET GYNECOL 1959;77: 772-9. 8. Newton M, Mosey LM, Egli GE, Gifford WB, Hull BS. Blood loss during delivery and immediately after delivery. Obstet GynecoI1961;17:9-18. 9. Gahres EE, Albert SN, Dodek SM. Intrapartum blood loss measured with Cr 51 -tagged erythrocytes. Obstet Gynecol 1962; 19:455-62.
Volume 167 Number 5
10. Queenan JT, Nakamoto M. Postpartum immunization: the hypothetical hazard of manual removal of the placenta. Obstet Gynecol 1964;23:392-5. 11. Schwartz WH, GroUe K. The use of prophylactic antibiotics in cesarean section. J Reprod Med 1981 ;26:595-9. 12. Morales Wl, Collins EM, Angel JL, Knuppel RA. Short course of antibiotic therapy in treatment of postpartum endomyometritis. AM J OBSTET GY:-IECOL 1989; 161 :56872.
Placental management methods at cesarean delivery
13. Soper DE, Kemmer CT, Conover WB. Abbreviated antibiotic therapy for the treatment of postpartum endometritis. Obstet Gynecol 1987;69:127-30. 14. McCurdy CM, Smith 1, Rutherford SE, Coddington CC. A prospective comparison of ticarcillin and clavulanic acid with gentamicin and clindamycin utilizing an abbreviated regimen in the therapy of postpartum paraendometritis. Am 1 Gynecol Health 1990;4:25-32.
Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis I. Efficacy results James M. Wheeler, MD, MPH: Judith D. Knittle, BS,c and James D. Miller, MDb.c Houston, Texas, and Rockford and Deerfield, Illinois OBJECTIVE: We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis. STUDY DESIGN: A double-blind randomized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis. Pretreatment and posttreatment endometriosis symptoms and signs were assessed with standardized methods. RESULTS: When compared with danazol, leuprolide depot caused a more rapid and profound suppression of estradiol. Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis, as well as the pain and tenderness associated with endometriosis. CONCLUSION: Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain. (AM J OBSTET GVNECOL 1992;167:1367-71.)
Key words: Endometriosis, leuprolide, depot, symptoms, treatment Endometriosis is one of the most common causes of pelvic pain and involuntary infertility in women.' Unfortunately, treatment of this disease in women desiring future childbearing continues to be disappointing: Surgical treatment is associated with high recurrence rates (up to 40% after 5 years"), and medical treatment is associated with a high likelihood of side effects and
From the Center for Reproductive Medicine and Surgery, Baylor College of Medicine and The Methodist Hospital,' the University of Illinois College of Medicine,' and TAP Research.' A complete listing of members of the Lupron Endometriosis Study Group appears at the end of the article. Supported in part by a grant from TAP Pharmaceuticals, Inc. Received for publication September 26, 1991; revised April 24, 1992; accepted April 29, 1992. Reprint requests: James D. Miller, MD, Department of Obstetrics and Gynecology, University of Illinois College of Medicine, 1400 Charles St., Rockford, IL 61104. 611 /39006
recurrence rates similar to those seen with surgery.' Three drugs have received Food and Drug Administration (FDA) approval for treatment of women with endometriosis: danazol, depot leuprolide, and intranasal nafarelin. Intranasal administration of a gonadotropin-releasing hormone (GnRH) agonist was proved efficacious in treating symptomatic endometriosis· by suppressing endogenous estradiol production, with resulting atrophy of uterine and ectopic endometrial tissue. Previously, GnRH agonist administration has required multiple daily injections or intranasal inhalations twice daily; concerns with compliance have resulted from these frequent dosing requirements. A depot form of GnRH agonist, Lupron Depot 3.75 mg (leuprolide acetate for depot suspension), provides continuous release of drug over a 4-week period when administered as a monthly intramuscular injection. For women with endometriosis, the depot formulation 1367
Volume 167 Number 5
17.
18. 19. 20.
21.
Major basic protein as a predictor of preterm labor: a preliminary report. AM J OBSTET GYNECOL 1987;156: 790-6. Filley WV, Holley KE, Kephart GM, Gleich GJ. Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma. Lancet 1982;2:11-6. Peters MS, Schroeter AL, Kephart GM, Gleich GJ. Localization of eosinophil granule major basic protein in chronic urticaria. J Invest Derm 1983;81 :39-43. Krenik KD, Kephart GM, Offord KP, Dunnette SL, Gleich GJ. Comparison of antifading agents used in immunofluorescence. J Immunol Methods 1989; 117:91-7. Wassom DL, Loegering DA, Solley GO, et al. Elevated serum levels of the eosinophil granule major basic protein in patients with eosinophilia. J Clin Invest 1981:67:65161. McConahey PJ, Dixon FJ. A method of trace iodination
22.
23. 24. 25.
of proteins for immunologic studies. Int Arch Allergy Appl Immunol 1966;29:185-9. Nelson DM, Crouch EC, Curran EM, Farmer DR. Trophoblast interaction with fibrin matrix: epithelialization of peri villous fibrin deposits as a mechanism for villous repair in the human placenta. AmJ Patho11990; 136:85565. Davies BR, Casanueva E, Arroyo P. Placentas of smallfor-dates infants: a small controlled series from Mexico City, Mexico. AMJ OBSTET GY:--IECOL 1984;149:731-6. Altshuler G, Russell P, Ermocilla R. The placental pathology of small-for-gestational age infants. A~ J OBSTET GYNECOL 1975;121:351-9. De Lia JE. Placenta and fetal development. In: Scott JR, DiSaia PJ, Hammond CB, Spellacy WN, eds. Danforth's obstetrics and gynecology. Philadelphia: JB Lippincott. 1990: 101.
The effect of placental management at cesarean delivery on operative blood loss Charles M. McCurdy, Jr., MD, Everett F. Magann, MD, Cynthia J. McCurdy, MD, and Andrew K. Saltzman, MD Camp Lejeune, North Carolina OBJECTIVES: The effect of alternative methods of placental delivery at cesarean section on blood loss has not been reported. The hypothesis of this study was that spontaneous expUlsion of the placenta would reduce operative blood loss, compared with that of manual extraction during cesarean delivery. STUDY DESIGN: We prospectively randomized and compared outcomes of 62 gravid women with manual (n = 31) or spontaneous (n = 31) placental delivery at cesarean section. Operative blood loss was measured directly. RESULTS: Blood loss measured at cesarean delivery was greater in the manually delivered group (967 ± 248 ml) than in the spontaneously delivered group (666 ± 271 ml, p < 0.0001). The incidence of postpartum endometritis was sevenfold greater in the manual than the spontaneous group (23% vs 3%, respectively; p < 0.05). CONCLUSIONS: We conclude that spontaneous expUlsion of the placenta at cesarean delivery results in less operative blood loss and a lower incidence of postoperative endometritis. (AM J OBSTET GYNECOL 1992;167:1363-7.)
Key words: Cesarean delivery, placenta, blood loss Cesarean delivery is one of the most commonly performed major operations in the United States. Patients undergoing abdominal delivery are exposed not only From the Department of Obstetrics and Gynecology, Naval Hospital Camp Lejeune. This article represents the findings of the authors and is not necessarily the opinions of the United States Government. Received for publication November 18, 1991; revised March 18, 1992; accepted March 31,1992. Reprint requests: Charles M. McCurdy, Jr., MD, Department of Obstetrics and Gynecology, University of Arizona, Health Sciences Center, 1501 Campbell Ave., Tucson, AZ 85724.
6/1138211
to risks inherent to major abdominal surgery but to additional risks (e.g., thromboembolic phenomena, aspiration pneumonia) in association with physiologic alterations of pregnancy. At term the gravid uterus is perfused at a rate of 500 to 750 mllmin.! This physiologic hyperperfusion results in an average blood loss at cesarean deE very of approximately 1000 ml and a risk for operative hemorrhage." Infectious morbidity is estimated at 5% to 85% in postcesarean patients." Studies of the possible role the technique of placental delivery might play in operative blood loss at cesarean delivery have not been reported. In texts of operative
1364
McCurdy et al.
obstetrics that address placental delivery, a manual shearing of the placenta from its attachment at the decidua basalis after delivery of the fetus is suggested. Spontaneous expulsion of the placenta is not discouraged unless occurring in an untimely fashion!' 5 We prospectively examined the effect of placental management on operative blood loss at cesarean delivery. We hypothesized that spontaneous delivery of the placenta, similar to that during vaginal deliveries, would reduce blood loss and would not be associated with a significantly prolonged duration of surgery. Methods
This prospective study was performed in 62 women undergoing cesarean delivery at Naval Hospital Camp Lejeune between September 1990 and March 1991. Regional and institutional research review board approval was obtained for the study, as was written informed consent from all volunteers. Sixty-two patients who were candidates for cesarean delivery were preoperatively enrolled consecutively and assigned randomly to study or control groups by randomized cards in numerically ordered and sealed envelopes. The study group was that group of patients having spontaneous expulsion of the placenta at cesarean delivery. The control group consisted of those patients with manual detachment of the placenta at cesarean delivery. Patients 15,000/ml), and at least two temperature elevations (~38° C) >6 hours apart) after the first 24 hours post partum. Data on all 62 patients enrolled were available for review with no postenrollment exclusions from this study. Statistical analysis of continuous data was by the two-tailed Student t test. Discrete data were analyzed via analysis of variance. Statistical significance was set for values of p < 0.05. Results
Demographic characteristics of all patients are compared in Table I. Parity and ethnicity were not significantly different in this study. There was no significant differences between the two groups for antenatal complications of hypertension, postdatism, diabetes, bleeding disorders, obesity, fetal growth disorders, and antenatal assessment outcomes. Indications for cesarean delivery included: arrest of labor (50%), fetal malpresentation (18%), fetal distress (6%), active genital herpes (5%), and elective repeat cesarean delivery (21 %). No differences existed between the groups for indications for cesarean delivery. Other preoperative comparisons are reported in Table II. In addition to oxytocin, four patients had been treated with terbutaline, three with prostaglandin E2 gel, and five received magnesium sulfate with no statistically significant differences between the groups. Amniotic fluid index determined preoperatively did not vary significantly. Labor occurred in 18 of 31 and 20 of 31 patients in the study and control groups, respectively (not significant). Rupture of the membranes was documented in 14 of 31 patients having spontaneous expulsion and 18 of31 patients undergoing manual extraction of the placenta (not significant).
Placental management methods at cesarean delivery
Volume 167 Number 5
Table I. Patient demographics
Table III. Operative data Placental delivery
spontaneous (N = 31)
Age (yr) Gravidity Gestational age (wk) Weight (kg) Admission hemoglobin (gm/dl)
24.2 1.9 38.6 81.2 12.5
5.5 1.0 2.4 ± 6.8 ± 1.0 ±
± ±
Placental delivery
Manual (N = 31)
24.5 1.8 39.6 79.5 12.0
4.0 1.0 ± 1.4 ± 5.1 ± 2.5 ±
±
Data are presented as mean ± SD. p, Not significant.
Table II. Preoperative data Placental delivery
Presence of labor (No.) Oxytocin use (No.) Primary cesarean delivery (No.) Amniotic fluid index (cm)
1365
Spontaneous (N = 31)
Manual (N = 31)
18 (58%)
20 (65%)
13 (42%) 21 (68%)
14 (45%) 25 (81 %)
10.5 ± 3.9
Spontaneous (N = 31)
Duration of surgery (min) Uterine incision "open" (min) Duration of stage III (min) Measured blood loss (ml) Estimated blood loss (ml)
The incidence of regional anesthesia was not significantly different (25/31 [81 %] in the spontaneous group and 23/31 [74%] in the manual placental delivery group). Antibiotic prophylaxis for obstetric and medical indications was given in 22 of 31 (71 %) and 24 of 31 (77%) for the spontaneous and manual groups, respectively (not significant). Abdominal incisions were transverse in 29 of 31 and 30 of 31 patients in the spontaneous and manual groups, respectively. Additionally, transverse uterine incisions were performed in 30 of 31 and all of the 31 patients in the two respective groups (not significant). Comparative operative data are listed in Table III. Tubal ligation was performed in an equal number of patients in the study and control groups (n = 5 in each). Again, uterine incision "open" refers to length of time recorded from initiation of uterine incision to completion of imbricating layer. Measured blood loss was significantly greater in the manually detached placenta group than in the spontaneously delivered placenta group (p < 0.0001). Estimated blood loss was greater in the manually detached group than in the spontaneously delivered group (p < 0.05). Surgical complications were sporadic and included: uterine atony (n = 1), uterine incisional extension (n = 1), and aspiration pneumonia (n = 1). There was no difference between the study groups regarding the incidence of surgical complications. Postoperative data including decrease in hemoglobin
32.7 ± 6.3
35.1 ± 8.4
13.0 ± 3.7
12.9
±
3.4
2.0 ± 0.9
1.6 ± 0.9
666 ± 271*
967 ± 248
764 ± 228t
924 ± 304
*p < 0.0001, compared with control. tp < 0.05, compared with control.
Table IV. Postoperative data Placental delivery
10.3 ± 3.7
p, Not significant.
Manual (control) (N = 31)
Decrease in hemoglobin (gm/dl) 12 hr after operation 48 hr after operation Postoperative hospital stay (days) Incidence of endometritis (No.) Incidence of other complications (No.)
Spontaneous (N = 31)
Manual (control) (N = 31)
1.2 ± 0.9 1.4 ± 0.8* 3.9 ± 1.1*
1.5 ± 0.9 1.9 ± 0.8 4.8 ± 2.1
1 (3%)*
7 (23%)
3 (10%)
2 (6%)
*p < 0.05, compared with controls. at 12 and 48 hours are reported in Table IV. No significant difference existed at 12 hours; however, the decrease in postoperative hemoglobin was significantly greater in the group with manual removal than in the spontaneous expulsion group at 48 hours. In addition, the incidence of puerperal endometritis was sevenfold higher in the manual group. Postoperative hospital stay was also significantly longer in the group undergoing manual placental delivery. The incidence of other complications including wound infection (n = 2), urinary tract infection (n = 2), and transfusion (n = 1) was not statistically different in the two groups.
Comment In this study a significant decrease in measured blood loss was seen in patients undergoing cesarean delivery in whom the placenta was spontaneously, rather than manually, removed. Additional support for greater blood loss in the manual placental delivery group was found with a significantly greater decrease in hemoglobin concentration at 48 hours after operation (1.9
1366 McCurdy et al.
vs 1.4 gm/dl). The duration of surgery, duration of operative stage III, and length of time the uterine incision was open were not altered by the mode of placental delivery. Measured blood loss at delivery, vaginal or cesarean, has been compared by hemodilutional spectrophotometric assays and radiochromium-labeled red blood cell assays.2. 7-9 In this study blood loss was measured by volume and gravimetric assessment. A few alterations in our technique deserve attention. Initially, the use of the 10 Ban-drape laparotomy drape must be considered. This recent innovation in the management of excess body fluids at abdominal surgery allows as well for the more thorough collection of all fluids not absorbed by laparotomy packs. Measurement of collected fluid, dry and wet pack weight, and all irrigation fluids should then give an accurate estimate of the true operative blood loss. The second problem encountered in measuring blood loss at delivery is the confounding factor of an undetermined volume of amniotic fluid. Preoperative amniotic fluid index assessment was used to correct for amniotic fluid volumes. Although amniotic fluid index is a semiquantitative method of assessing amniotic fluid volume, the absence of a significant difference between the mean amniotic fluid index values of the study groups suggests that the volumes of amniotic fluid collected at cesarean delivery were similar in the two groups. This amniotic fluid volume may lead to an overestimation of measured blood loss. After vaginal delivery endogenous oxytocin is released, myometrial cells shorten, and the placental implantation site involutes. This process also occludes vessellumina, thus diminishing blood flow to the decidua basalis. Placental cleavage occurs when a relatively fixed placental surface area is implanted over an involuting site. A retroplacental hematoma forms and is confined by the remaining placental attachments; this results in a hydrostatic effect on acute blood loss at the implantation bed. Vasospasm and local involvement of the coagulation cascade also lead to hemostasis. This is clinically evident after vaginal birth by the palpation of a firm, involuted uterine fundus at about the level of the umbilicus. At cesarean birth the tendency of the uterus to undergo similar changes may be appreciated both visibly and by palpation, before actual delivery of the placenta. Manual shearing of the placenta from the decidua basalis before significant involution of the implantation bed theoretically would result in unaltered perfusion to this area and increased blood loss. A qualitative disadvantage to manual placental extraction was proposed by Queenan and Nakamoto,IO who noted an increased rate of rhesus factor isoimmunization after this method of placental delivery. In the current study an increased rate of postoperative uterine infection followed manual placental delivery
November 1992 Am J Obstet Gynecol
(23% vs 3%). The relatively high incidence of endometritis after manual extraction noted in this study is in concordance with recent published trends of the incidence of postcesarean endometritis ranging from 20% to 38% and the range of postoperative infectious morbidity existing in the literature." 12 Military studies have typically demonstrated a lower incidence of this entity, consistent with the overall incidence of 13% noted in this study. 13. 14 Tissue trauma, maternal autotransfusion of bacterially contaminated blood before implantation site involution, surgical contamination, and excessive blood loss are possible explanations for this finding. This concomitant increased postoperative hospital stay in patients undergoing manual placental extraction was related to the increased incidence of endometritis and subsequent duration of antibiotic therapy. Although not demonstrated in this study, spontaneous delivery of the placenta may be of benefit in cases of pathologic placental implantation (e.g., placenta accreta, lower uterine segment placental implantation) where maximal decrease in implantation bed surface area and spiral artery perfusion pressure would be desirable. In conclusion, spontaneous expulsion of the placenta at cesarean delivery was associated with decreases in surgical blood loss as measured and assessed by change in hemoglobin concentrations. Incidence of postoperative endometritis and consequent prolonged hospital stay were also reduced in women in whom this surgical technique was used.
REFERENCES I. Assali NS, Douglas RA, Baird WW. Measurement of uterine blood flow and uterine metabolism. AM] OB8TET GyNECOL 1953;66:248-53. 2. Pritchard ]A, Baldwin RM, Dickey ]C, Wiggins KM. Blood volume changes in pregnancy and the puerperium. II. Red cell loss and changes in apparent blood volume during and following vaginal delivery, cesarean section, and cesarean section plus total hysterectomy. AM] OB8TET GYNECOL 1962;84:1271-82. 3. Duff P. Pathophysiology and management of postcesarean endomyometritis. Obstet Gynecol 1986;67:269-75. 4. Phelan ]P, Clark SL. Cesarean delivery: the transperitoneal approach. In: Phelan ]P, Clark SL, eds. Cesarean delivery. New York: Elsevier, 1988:201-18. 5. Hibbard LT. Cesarean section and other surgical procedures. In: Gabbe SG, Niebyl ]R, Simpson ]L, eds. Obstetrics: normal and problem pregnancies. New York: Churchill Livingstone, 1986:517-48. 6. Phelan]P, Smith CV, Broussard P, Small M. Amniotic fluid volume assessment with the four-quadrant technique at 36-42 weeks' gestation.] Reprod Med 1987;32:540-2. 7. Wilcox FC, Hunt AB, Owen CA. The measurement of blood lost during cesarean section. AM] OB8TET GYNECOL 1959;77: 772-9. 8. Newton M, Mosey LM, Egli GE, Gifford WB, Hull BS. Blood loss during delivery and immediately after delivery. Obstet GynecoI1961;17:9-18. 9. Gahres EE, Albert SN, Dodek SM. Intrapartum blood loss measured with Cr 51 -tagged erythrocytes. Obstet Gynecol 1962; 19:455-62.
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10. Queenan JT, Nakamoto M. Postpartum immunization: the hypothetical hazard of manual removal of the placenta. Obstet Gynecol 1964;23:392-5. 11. Schwartz WH, GroUe K. The use of prophylactic antibiotics in cesarean section. J Reprod Med 1981 ;26:595-9. 12. Morales Wl, Collins EM, Angel JL, Knuppel RA. Short course of antibiotic therapy in treatment of postpartum endomyometritis. AM J OBSTET GY:-IECOL 1989; 161 :56872.
Placental management methods at cesarean delivery
13. Soper DE, Kemmer CT, Conover WB. Abbreviated antibiotic therapy for the treatment of postpartum endometritis. Obstet Gynecol 1987;69:127-30. 14. McCurdy CM, Smith 1, Rutherford SE, Coddington CC. A prospective comparison of ticarcillin and clavulanic acid with gentamicin and clindamycin utilizing an abbreviated regimen in the therapy of postpartum paraendometritis. Am 1 Gynecol Health 1990;4:25-32.
Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis I. Efficacy results James M. Wheeler, MD, MPH: Judith D. Knittle, BS,c and James D. Miller, MDb.c Houston, Texas, and Rockford and Deerfield, Illinois OBJECTIVE: We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis. STUDY DESIGN: A double-blind randomized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis. Pretreatment and posttreatment endometriosis symptoms and signs were assessed with standardized methods. RESULTS: When compared with danazol, leuprolide depot caused a more rapid and profound suppression of estradiol. Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis, as well as the pain and tenderness associated with endometriosis. CONCLUSION: Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain. (AM J OBSTET GVNECOL 1992;167:1367-71.)
Key words: Endometriosis, leuprolide, depot, symptoms, treatment Endometriosis is one of the most common causes of pelvic pain and involuntary infertility in women.' Unfortunately, treatment of this disease in women desiring future childbearing continues to be disappointing: Surgical treatment is associated with high recurrence rates (up to 40% after 5 years"), and medical treatment is associated with a high likelihood of side effects and
From the Center for Reproductive Medicine and Surgery, Baylor College of Medicine and The Methodist Hospital,' the University of Illinois College of Medicine,' and TAP Research.' A complete listing of members of the Lupron Endometriosis Study Group appears at the end of the article. Supported in part by a grant from TAP Pharmaceuticals, Inc. Received for publication September 26, 1991; revised April 24, 1992; accepted April 29, 1992. Reprint requests: James D. Miller, MD, Department of Obstetrics and Gynecology, University of Illinois College of Medicine, 1400 Charles St., Rockford, IL 61104. 611 /39006
recurrence rates similar to those seen with surgery.' Three drugs have received Food and Drug Administration (FDA) approval for treatment of women with endometriosis: danazol, depot leuprolide, and intranasal nafarelin. Intranasal administration of a gonadotropin-releasing hormone (GnRH) agonist was proved efficacious in treating symptomatic endometriosis· by suppressing endogenous estradiol production, with resulting atrophy of uterine and ectopic endometrial tissue. Previously, GnRH agonist administration has required multiple daily injections or intranasal inhalations twice daily; concerns with compliance have resulted from these frequent dosing requirements. A depot form of GnRH agonist, Lupron Depot 3.75 mg (leuprolide acetate for depot suspension), provides continuous release of drug over a 4-week period when administered as a monthly intramuscular injection. For women with endometriosis, the depot formulation 1367
