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Placenta accreta leads to hemorrhage
Sally is a 27-year-old gravida with 1 prior cesarean whose ultrasound imaging is suspicious for “placenta adherent to the bladder.” At 38 weeks, she delivers a viable infant by classical cesarean, at which time the ultrasound finding is confirmed: the placenta is densely adherent.
The placenta is left in situ, no methotrexate is given, and Sally is followed with clotting studies and exams.
Eight weeks later, when her fibrinogen level falls and the prothrombin time and partial thromboplastin time become abnormal, the obstetrician attempts to perform dilatation and evacuation, but massive bleeding ensues. The physician then performs a total abdominal hysterectomy, but bleeding continues from the cuff.
What is the best way to manage the hemorrhage?
After identifying its source, the surgeon should apply pressure to abate the bleeding, using packing if necessary, and repair the affected artery or vein. Fortunately, we have many tools at our disposal, from preventive steps like careful preoperative assessment to the use of hemostatic agents, fibrin glues, hypogastric artery ligation, and specialized pelvic packing techniques. With prompt action and a stepwise approach, this bona fide catastrophe can usually be successfully managed. This article details a 5-step action plan.
If massive bleeding occurs during laparoscopic or vaginal surgery, a laparotomy may be indicated, and intraoperative management would follow the same 5 steps.
STEP 1Like the Boy Scouts, Be Prepared
Although surgeons are acutely aware that drugs such as warfarin and heparin can cause intraoperative bleeding, the patient history and predisposing factors sometimes get short shrift.
Besides asking about the patient’s medications, assess the following:
- Platelets. The primary laboratory test to evaluate potential bleeding is the platelet count. In general, 10,000 to 20,000 platelets are needed for hemostasis. However, 50,000 are needed for any surgery or invasive procedure, such as insertion of a central line.1 I recommend platelet evaluation for patients scheduled for major abdominal surgery.
- History of bleeding. If the patient or her family has a history of bleeding with any surgery, evaluate her for von Willebrand’s disease.
- High alcohol intake warrants preoperative liver function and coagulation studies.
- Some herbal or natural remedies can exacerbate intraoperative hemorrhage through their inhibition of coagulation, especially the agents listed in TABLE 1. They should generally be discontinued 2 to 7 days before surgery.2
- Aspirin and nonsteroidal anti-inflammatory drugs should be discontinued 7 days before anticipated surgery. However, patients may continue aspirin at a daily dose of 81 mg.
- Poor nutrition and obesity predispose the patient to wound complications and intraoperative bleeding. Patients who are severely malnourished can take dietary supplements or receive total parenteral nutrition prior to surgery.
- Intraoperative factors such as the 3 “inadequacies” (inadequate incision, retraction, and anesthesia), low core body temperature, severe adhesions (ie, endometriosis), and large vascular tumors also are sometimes associated with bleeding.
TABLE 1
Alternative remedies that may exacerbate bleeding
- 32% to 37% of Americans use these remedies, but only 38% of them tell their doctor
- Stop all alternative remedies 2 to 7 days before surgery
| REMEDY | USED FOR | PERIOPERATIVE RISKS |
|---|---|---|
| Beta-carotene | Vitamin A precursor; often taken as a nutritional supplement | May cause coagulopathy |
| Feverfew | Used to prevent or treat migraine and ease menstrual cramps | May inhibit coagulation |
| Fish oil | Rich in omega-3 fatty acids, recommended for cardiovascular health | Omega-3s inhibit coagulation |
| Garlic | Used to reduce hypertension and high cholesterol | Case reports of unexpected or increased surgical bleeding, prolonged bleeding time, and impaired platelet aggregation |
| Ginkgo | Treatment of dementia, impaired cognition, and memory | Various ginkgolides have platelet-activating-factor antagonist properties; case reports of spontaneous bleeding |
| Ginseng | Widely used as a stimulant, tonic, diuretic, mood elevator, and energy booster | May cause hypertension, cardiovascular instability, coagulopathy, and sedation |
| St. John’s wort | Antidepressant | May cause cardiovascular instability, coagulopathy, and sedation |
| Vitamin E | Antioxidant | May interfere with coagulation |
STEP 2Follow These Basic Principles
Whenever bleeding is encountered in any area of the abdominal cavity, the first step is simple: Apply immediate pressure with a finger or sponge stick. Then obtain exposure and assistance. Exposure usually means extending the incision and using a fixed table retractor.
If the source of bleeding is unknown, apply pressure on the aorta using a hand, weighted speculum, or Conn aortic compressor (Pilling-branded, Teleflex Medical, Limerick, Pa).
Secure individual vessels with finetipped clamps and small-caliber sutures or clips, and minimize the use of clamps. Never place clamps or sutures blindly, and never use electrocautery for large lacerations.
If you choose to use packs to temporarily control bleeding, insert them carefully to avoid tearing veins, and place pelvic packs (hot or cold) in a stepwise fashion, from sidewall to sidewall. Leave packs in place for at least 15 minutes and remove them sequentially.
Great vessel injuries
The aorta, vena cava, and common iliac vessels are sometimes injured during removal of paraaortic nodes or when the inferior mesenteric vessels are avulsed during retraction of the sigmoid colon. In addition, needle or trocar injuries during operative laparoscopy occur in as many as 4 of every 10,000 procedures.3
Again, the first step in managing great vessel injuries is applying pressure. Then obtain blood components, and, if necessary, consult with a vascular surgeon or gynecologic oncologist.
In general, once the patient is hemodynamically stable, the affected vessel should be compressed proximally and distally. Use Allis or vascular clamps on the torn edges to elevate the lacerated area. My preference is to close these injuries with a running 5-0 or 6-0 nylon or monofilament polypropylene (MFPP) suture on a cardiovascular needle.
Replacing blood and its components
Be aware of the following replacement guidelines for catastrophic intraoperative hemorrhage:
- For every 8 U of red blood cells replaced, give 2 U of fresh frozen plasma.
- If more than 10 U of red blood cells are replaced, give 10 U of platelets, preferably at the end of the procedure.
- With prolonged PTT, give fresh frozen plasma.
- If fibrinogen is low, give 2 U of cryoprecipitate.1
When massive bleeding is anticipated or encountered, the Haemonetics Cell Saver (Haemonetics Corp, Braintree, Mass) is invaluable. This device, which requires a trained technician, removes blood from the operative field, anticoagulates it, and washes red blood cells, which are infused. It is accepted by many Jehovah’s Witnesses,4 and has been used safely in women with cesarean-associated bleeding.5 Relative contraindications include malignancy and bacterial contamination from a ruptured abscess or inadvertent injury to unprepared bowel.6 The Cell Saver may be used after heavy bleeding from hysterectomy or in patients with ruptured membranes.
STEP 3Try A Topical Hemostatic Agent
If hemorrhage contiues after arterial bleeders are secured, consider a topical hemostatic agent (TABLE 2). All such agents require pressure to be applied for 3 to 5 minutes.
My preferences are Surgicel (Johnson & Johnson, New Brunswick, NJ) and Gelfoam (Pharmacia, Kalamazoo, Mich). In general, Avitene Ultrafoam collagen hemostat (Davol, subsidiary of C.R. Bard, Murray Hill, NJ) works poorly in the presence of thrombocytopenia and should be used with caution near the ureter.
Fibrin glue has been widely used as a hemostatic agent in microvascular, cardiovascular, and thoracic surgery.
To prepare fibrin glue at my institution, we use a double-barrel syringe to apply equal amounts of cryoprecipitate and thrombin at the same time. One fibrin sealant, Tisseal VH (Baxter Healthcare, Deerfield, Ill), comes with a Duploject applicator. After the agent is thoroughly applied (it is sprayed), pressure is applied for 3 to 5 minutes.
The same manufacturer also produces Coseal, which is used in vascular reconstruction to achieve additional hemostasis by mechanically sealing off areas of leakage, and Floseal, to help achieve hemostasis when ligatures or clips are impractical.
TABLE 2
Topical intraperitoneal hemostatic agents
| AGENT | WHAT IT IS | HOW IT IS APPLIED |
|---|---|---|
| Avitene Ultrafoam | Absorbable collagen hemostat | Comes in powder; sprinkle on area |
Fibrin glue
| Equal amounts of cryoprecipitate and thrombin | Spray on affected area with double-barrel syringe or device supplied by Baxter Healthcare |
| Gelfoam | Absorbable gelatin sponge | Cut in strips of appropriate size and apply to area |
| Surgicel | Oxidized regenerated cellulose | Cut in strips of appropriate size and apply to area |
STEP 4Hypogastric Artery Ligation
SALLY’S CASE
Bleeding persists
Because of the hemorrhage, a gynecologic oncology consult is obtained and the hypogastric artery is ligated bilaterally, but bleeding continues. During further exploration, the left ureter is found to be ligated. Sally receives 65 U of packed red blood cells, platelets, and fresh frozen plasma. The Cell Saver also is used.
If pelvic oozing persists after application of a topical hemostatic agent, consider hypogastric artery ligation, which controls pelvic hemorrhage in as many as 50% of patients.7,8
STEP 5When All Else Fails: “Pack And Go”
If intraoperative bleeding persists despite hypogastric artery ligation and the other measures, the life-saving modality of choice is a pelvic pack left in place 2 to 3 days. I prefer a fast, simple method: “pack and go” or damage-control technique.10-12
A 2- to 4-inch Kerlix gauze (Kendall Health Care Products, Mansfield, Mass) is tightly packed over a fibrin glue bed from side to side in the pelvis. Only the skin is closed using towel clips or a running suture. The patient is immediately transferred to intensive care, where acidosis, coagulopathy, and hypothermia are corrected. In 48 to 72 hours, the packs are gently removed with saline drip assistance. If hemostasis still has not been achieved, repacking is an option.
Presacral venous bleeding
Two helpful methods to quell presacral venous bleeding are:
- inserting stainless steel thumbtacks
- indirect coagulation through a muscle fragment
The thumbtack method
The presacral veins are sometimes injured during presacral neurectomy, sacrocolpopexy, or posterior exenteration. This bleeding can be controlled by inserting stainless steel thumbtacks, with direct pressure from the surgeon’s hand, directly into the sacrum.15-17 These work by compressing veins adjacent to the bone, and are left in place permanently. No complications have been reported.
Indirect coagulation
Another method of controlling presacral venous bleeding is indirect coagulation through a muscle fragment. This is done by harvesting a 2 x 1 cm piece of muscle from the rectus abdominus and pressing it against the bleeding veins. Then set a Bovie (Valley Lab, Boulder, Colo) at 40 W of pure cutting current and apply it to the muscle fragment for 1 to 2 minutes. This method has been successful in 12 of 12 reported cases.18,19
Other methods of controlling presacral venous bleeding include bipolar cautery, use of bone wax, and suturing in “sandwiches” of Avitene alternated with Gelfoam, but these strategies have met with limited success.
Pelvic hemorrhage
Arterial embolization
Angiographic insertion of Gelfoam pledgets or Silastic coils may effectively control pelvic hemorrhage in up to 90% of postpartum and postoperative patients.20,21 Hypogastric artery embolization can also be done intraoperatively.22
However, this technique should be used with caution, as it may require 1 to 2 hours to perform and is inappropriate for patients with hypovolemic shock. Complications are rare, but can occur in up to 6% to 7% of patients.21 They include postoperative fever, pelvic abscess formation, reflux of embolic material, nontarget embolization, foot and buttocks ischemia, bladder and rectal wall necrosis, and late rebleeding.
Arterial embolization does not appear to affect subsequent pregnancies.23
Military antishock trousers The MAST or aviation “G” suit is sometimes used as an intermediate step to laparotomy in patients with ectopic pregnancy or postoperative or postpartum hemorrhage.24 Its major use is to stabilize patients for surgery by compressing peripheral circulation, thereby diverting blood to the core circulation.
Inflate the legs first, then the abdomen; leave the MAST suit in place for 2 to 48 hours; and deflate in reverse order.
Contraindications include pulmonary edema, cardiogenic shock, rupture of the diaphragm, and pregnancy.
SALLY’S CASE
Hemorrhage abates
A “pack and go” technique is used to control bleeding. The fascia is left open, and the skin is closed with towel clips over the tight pelvic pack. Sally is sent to the ICU, where clotting parameters are corrected.
She undergoes reoperation 36 hours later, at which time no bleeding is encountered.
The left ureter is reimplanted into the bladder, and she makes a full recovery.
The author has served on the speakers bureau for Wyeth.
1. Nolan TE, Gallup DG. Massive transfusion: a current review. Obstet Gynecol Surv. 1991;46:289-295
2. Ang-Lee MK, Moss J, Yuan C-S. Herbal medicine and preoperative care. JAMA. 2001;286:208-216.
3. Härkü-Siren P, Sjöberg J, Kurki T. Major complications of laparoscopy: a follow-up Finnish study. Obstet Gynecol. 1999;94:94-98.
4. deCastro RM. Bloodless surgery: establishment of a program for the special needs of the Jehovah’s Witness community: the gynecologic surgery experience at a community hospital. Obstet Gynecol. 1999;180:149-158.
5. Rebarber A, Lonser R, Jackson S, Copel JA, Siple S. The safety of intraoperative blood collection and autotransfusion during cesarean section. Am J Obstet Gynecol. 1998;169:715-720.
6. Klimberg I, Sirois R, Wajsman Z, Baker J. Intraoperative autotransfusion in urologic oncology Arch Surg. 1986;121:1326-1329.
7. Clark SL, Phelan JP, Yeh Z-Y, Bruce SR, Paul RH. Hypogastric artery ligation for obstetric hemorrhage. Obstet Gynecol. 1985;66:353-356.
8. Thavarash AS, Sivalingam N, Almohdzar SA. Internal iliac and ovarian artery ligation in the control of pelvic hemorrhage. Aust N Z J Obstet Gynecol. 1989;29:22-25.
9. Burchell RC. Internal iliac ligation. Haemodynamics. Obstet Gynecol. 1964;5:53-59.
10. Finan MA, Fiorica JV, Hoffman MS, et al. Massive pelvic hemorrhage during gynecologic cancer surgery: “pack and go back.” Gynecol Oncol. 1996;62:390-395.
11. Rotondo MF, Zonies DH. The damage control sequence and underlying logic. Surg Clin N Am. 1997;77:761-777.
12. Inge JA, Gallup DG, Davis FE. Catastrophic hemorrhage from placenta previa-accreta. A case series and guidelines for management. J Pelvic Surg. 2000;6:268-272.
13. Cassels JW Jr, Greenberg H, Otterson WN. Pelvic tamponade in puerperal hemorrhage. J Reprod Med. 1985;30:689-692.
14. Hallack M, Didly GA, III, Hurley TJ, Moise KJ, Jr. Transvaginal pressure pack for life-threatening pelvis hemorrhage secondary to placenta accreta. Obstet Gynecol. 1991;78:938-940.
15. Khan FA, Fang DT, Nivatvongs S. Management of presacral hemorrhage during rectal resection. Surg Gynecol Obstet. 1987;165:275-277.
16. Pastner B, Orr JW. Intractable venous hemorrhage: use of stainless steel thumbtacks to obtain hemostasis. Am J Obstet Gynecol. 1990;162:452-455.
17. Timmons MC, Kohler MF, Addison WA. Thumbtack use for control of presacral bleeding with description of an instrument for thumbtack application. Obstet Gynecol. 1991;78:313-315.
18. Xu J, Lin J. Control of presacral hemorrhage with electrocautery through a muscle fragment pressed on the bleeding vein. J Am Coll Surg. 1994;179:351-354.
19. Miklos JR, Kohli N, Sze EH. Control of presacral hemorrhage using indirect coagulation through a muscle fragment. J Pelvic Surg. 1996;2:268-270.
20. Hansch E, Chitkara U, McAlpine J, El-Sayed Y, Dake MD, Razavi MK. Pelvic arterial embolization for control of obstetric hemorrhage: a five-year experience. Obstet Gynecol. 1999;180:1454-1460.
21. Verdantham S, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization: an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol. 1997;176:938-946.
22. Saueracker AJ, McCroskey BL, Moor EE, Moore FA. Intraoperative hypogastric artery embolization for life-threatening pelvic hemorrhage: a preliminary report. J Trauma. 1987;27:1127-1129.
23. Orman D, White R, Pollak J, Tal M. Pelvic embolization for intractable postpartum hemorrhage: long-term follow-up and implications for fertility. Obstet Gynecol. 2003;102:904-910.
24. Pearse CS, Magrina JF, Finley BE. Use of MAST suit in obstetrics and gynecology. Obstet Gynecol Surv. 1984;39:416-422.
Placenta accreta leads to hemorrhage
Sally is a 27-year-old gravida with 1 prior cesarean whose ultrasound imaging is suspicious for “placenta adherent to the bladder.” At 38 weeks, she delivers a viable infant by classical cesarean, at which time the ultrasound finding is confirmed: the placenta is densely adherent.
The placenta is left in situ, no methotrexate is given, and Sally is followed with clotting studies and exams.
Eight weeks later, when her fibrinogen level falls and the prothrombin time and partial thromboplastin time become abnormal, the obstetrician attempts to perform dilatation and evacuation, but massive bleeding ensues. The physician then performs a total abdominal hysterectomy, but bleeding continues from the cuff.
What is the best way to manage the hemorrhage?
After identifying its source, the surgeon should apply pressure to abate the bleeding, using packing if necessary, and repair the affected artery or vein. Fortunately, we have many tools at our disposal, from preventive steps like careful preoperative assessment to the use of hemostatic agents, fibrin glues, hypogastric artery ligation, and specialized pelvic packing techniques. With prompt action and a stepwise approach, this bona fide catastrophe can usually be successfully managed. This article details a 5-step action plan.
If massive bleeding occurs during laparoscopic or vaginal surgery, a laparotomy may be indicated, and intraoperative management would follow the same 5 steps.
STEP 1Like the Boy Scouts, Be Prepared
Although surgeons are acutely aware that drugs such as warfarin and heparin can cause intraoperative bleeding, the patient history and predisposing factors sometimes get short shrift.
Besides asking about the patient’s medications, assess the following:
- Platelets. The primary laboratory test to evaluate potential bleeding is the platelet count. In general, 10,000 to 20,000 platelets are needed for hemostasis. However, 50,000 are needed for any surgery or invasive procedure, such as insertion of a central line.1 I recommend platelet evaluation for patients scheduled for major abdominal surgery.
- History of bleeding. If the patient or her family has a history of bleeding with any surgery, evaluate her for von Willebrand’s disease.
- High alcohol intake warrants preoperative liver function and coagulation studies.
- Some herbal or natural remedies can exacerbate intraoperative hemorrhage through their inhibition of coagulation, especially the agents listed in TABLE 1. They should generally be discontinued 2 to 7 days before surgery.2
- Aspirin and nonsteroidal anti-inflammatory drugs should be discontinued 7 days before anticipated surgery. However, patients may continue aspirin at a daily dose of 81 mg.
- Poor nutrition and obesity predispose the patient to wound complications and intraoperative bleeding. Patients who are severely malnourished can take dietary supplements or receive total parenteral nutrition prior to surgery.
- Intraoperative factors such as the 3 “inadequacies” (inadequate incision, retraction, and anesthesia), low core body temperature, severe adhesions (ie, endometriosis), and large vascular tumors also are sometimes associated with bleeding.
TABLE 1
Alternative remedies that may exacerbate bleeding
- 32% to 37% of Americans use these remedies, but only 38% of them tell their doctor
- Stop all alternative remedies 2 to 7 days before surgery
| REMEDY | USED FOR | PERIOPERATIVE RISKS |
|---|---|---|
| Beta-carotene | Vitamin A precursor; often taken as a nutritional supplement | May cause coagulopathy |
| Feverfew | Used to prevent or treat migraine and ease menstrual cramps | May inhibit coagulation |
| Fish oil | Rich in omega-3 fatty acids, recommended for cardiovascular health | Omega-3s inhibit coagulation |
| Garlic | Used to reduce hypertension and high cholesterol | Case reports of unexpected or increased surgical bleeding, prolonged bleeding time, and impaired platelet aggregation |
| Ginkgo | Treatment of dementia, impaired cognition, and memory | Various ginkgolides have platelet-activating-factor antagonist properties; case reports of spontaneous bleeding |
| Ginseng | Widely used as a stimulant, tonic, diuretic, mood elevator, and energy booster | May cause hypertension, cardiovascular instability, coagulopathy, and sedation |
| St. John’s wort | Antidepressant | May cause cardiovascular instability, coagulopathy, and sedation |
| Vitamin E | Antioxidant | May interfere with coagulation |
STEP 2Follow These Basic Principles
Whenever bleeding is encountered in any area of the abdominal cavity, the first step is simple: Apply immediate pressure with a finger or sponge stick. Then obtain exposure and assistance. Exposure usually means extending the incision and using a fixed table retractor.
If the source of bleeding is unknown, apply pressure on the aorta using a hand, weighted speculum, or Conn aortic compressor (Pilling-branded, Teleflex Medical, Limerick, Pa).
Secure individual vessels with finetipped clamps and small-caliber sutures or clips, and minimize the use of clamps. Never place clamps or sutures blindly, and never use electrocautery for large lacerations.
If you choose to use packs to temporarily control bleeding, insert them carefully to avoid tearing veins, and place pelvic packs (hot or cold) in a stepwise fashion, from sidewall to sidewall. Leave packs in place for at least 15 minutes and remove them sequentially.
Great vessel injuries
The aorta, vena cava, and common iliac vessels are sometimes injured during removal of paraaortic nodes or when the inferior mesenteric vessels are avulsed during retraction of the sigmoid colon. In addition, needle or trocar injuries during operative laparoscopy occur in as many as 4 of every 10,000 procedures.3
Again, the first step in managing great vessel injuries is applying pressure. Then obtain blood components, and, if necessary, consult with a vascular surgeon or gynecologic oncologist.
In general, once the patient is hemodynamically stable, the affected vessel should be compressed proximally and distally. Use Allis or vascular clamps on the torn edges to elevate the lacerated area. My preference is to close these injuries with a running 5-0 or 6-0 nylon or monofilament polypropylene (MFPP) suture on a cardiovascular needle.
Replacing blood and its components
Be aware of the following replacement guidelines for catastrophic intraoperative hemorrhage:
- For every 8 U of red blood cells replaced, give 2 U of fresh frozen plasma.
- If more than 10 U of red blood cells are replaced, give 10 U of platelets, preferably at the end of the procedure.
- With prolonged PTT, give fresh frozen plasma.
- If fibrinogen is low, give 2 U of cryoprecipitate.1
When massive bleeding is anticipated or encountered, the Haemonetics Cell Saver (Haemonetics Corp, Braintree, Mass) is invaluable. This device, which requires a trained technician, removes blood from the operative field, anticoagulates it, and washes red blood cells, which are infused. It is accepted by many Jehovah’s Witnesses,4 and has been used safely in women with cesarean-associated bleeding.5 Relative contraindications include malignancy and bacterial contamination from a ruptured abscess or inadvertent injury to unprepared bowel.6 The Cell Saver may be used after heavy bleeding from hysterectomy or in patients with ruptured membranes.
STEP 3Try A Topical Hemostatic Agent
If hemorrhage contiues after arterial bleeders are secured, consider a topical hemostatic agent (TABLE 2). All such agents require pressure to be applied for 3 to 5 minutes.
My preferences are Surgicel (Johnson & Johnson, New Brunswick, NJ) and Gelfoam (Pharmacia, Kalamazoo, Mich). In general, Avitene Ultrafoam collagen hemostat (Davol, subsidiary of C.R. Bard, Murray Hill, NJ) works poorly in the presence of thrombocytopenia and should be used with caution near the ureter.
Fibrin glue has been widely used as a hemostatic agent in microvascular, cardiovascular, and thoracic surgery.
To prepare fibrin glue at my institution, we use a double-barrel syringe to apply equal amounts of cryoprecipitate and thrombin at the same time. One fibrin sealant, Tisseal VH (Baxter Healthcare, Deerfield, Ill), comes with a Duploject applicator. After the agent is thoroughly applied (it is sprayed), pressure is applied for 3 to 5 minutes.
The same manufacturer also produces Coseal, which is used in vascular reconstruction to achieve additional hemostasis by mechanically sealing off areas of leakage, and Floseal, to help achieve hemostasis when ligatures or clips are impractical.
TABLE 2
Topical intraperitoneal hemostatic agents
| AGENT | WHAT IT IS | HOW IT IS APPLIED |
|---|---|---|
| Avitene Ultrafoam | Absorbable collagen hemostat | Comes in powder; sprinkle on area |
Fibrin glue
| Equal amounts of cryoprecipitate and thrombin | Spray on affected area with double-barrel syringe or device supplied by Baxter Healthcare |
| Gelfoam | Absorbable gelatin sponge | Cut in strips of appropriate size and apply to area |
| Surgicel | Oxidized regenerated cellulose | Cut in strips of appropriate size and apply to area |
STEP 4Hypogastric Artery Ligation
SALLY’S CASE
Bleeding persists
Because of the hemorrhage, a gynecologic oncology consult is obtained and the hypogastric artery is ligated bilaterally, but bleeding continues. During further exploration, the left ureter is found to be ligated. Sally receives 65 U of packed red blood cells, platelets, and fresh frozen plasma. The Cell Saver also is used.
If pelvic oozing persists after application of a topical hemostatic agent, consider hypogastric artery ligation, which controls pelvic hemorrhage in as many as 50% of patients.7,8
STEP 5When All Else Fails: “Pack And Go”
If intraoperative bleeding persists despite hypogastric artery ligation and the other measures, the life-saving modality of choice is a pelvic pack left in place 2 to 3 days. I prefer a fast, simple method: “pack and go” or damage-control technique.10-12
A 2- to 4-inch Kerlix gauze (Kendall Health Care Products, Mansfield, Mass) is tightly packed over a fibrin glue bed from side to side in the pelvis. Only the skin is closed using towel clips or a running suture. The patient is immediately transferred to intensive care, where acidosis, coagulopathy, and hypothermia are corrected. In 48 to 72 hours, the packs are gently removed with saline drip assistance. If hemostasis still has not been achieved, repacking is an option.
Presacral venous bleeding
Two helpful methods to quell presacral venous bleeding are:
- inserting stainless steel thumbtacks
- indirect coagulation through a muscle fragment
The thumbtack method
The presacral veins are sometimes injured during presacral neurectomy, sacrocolpopexy, or posterior exenteration. This bleeding can be controlled by inserting stainless steel thumbtacks, with direct pressure from the surgeon’s hand, directly into the sacrum.15-17 These work by compressing veins adjacent to the bone, and are left in place permanently. No complications have been reported.
Indirect coagulation
Another method of controlling presacral venous bleeding is indirect coagulation through a muscle fragment. This is done by harvesting a 2 x 1 cm piece of muscle from the rectus abdominus and pressing it against the bleeding veins. Then set a Bovie (Valley Lab, Boulder, Colo) at 40 W of pure cutting current and apply it to the muscle fragment for 1 to 2 minutes. This method has been successful in 12 of 12 reported cases.18,19
Other methods of controlling presacral venous bleeding include bipolar cautery, use of bone wax, and suturing in “sandwiches” of Avitene alternated with Gelfoam, but these strategies have met with limited success.
Pelvic hemorrhage
Arterial embolization
Angiographic insertion of Gelfoam pledgets or Silastic coils may effectively control pelvic hemorrhage in up to 90% of postpartum and postoperative patients.20,21 Hypogastric artery embolization can also be done intraoperatively.22
However, this technique should be used with caution, as it may require 1 to 2 hours to perform and is inappropriate for patients with hypovolemic shock. Complications are rare, but can occur in up to 6% to 7% of patients.21 They include postoperative fever, pelvic abscess formation, reflux of embolic material, nontarget embolization, foot and buttocks ischemia, bladder and rectal wall necrosis, and late rebleeding.
Arterial embolization does not appear to affect subsequent pregnancies.23
Military antishock trousers The MAST or aviation “G” suit is sometimes used as an intermediate step to laparotomy in patients with ectopic pregnancy or postoperative or postpartum hemorrhage.24 Its major use is to stabilize patients for surgery by compressing peripheral circulation, thereby diverting blood to the core circulation.
Inflate the legs first, then the abdomen; leave the MAST suit in place for 2 to 48 hours; and deflate in reverse order.
Contraindications include pulmonary edema, cardiogenic shock, rupture of the diaphragm, and pregnancy.
SALLY’S CASE
Hemorrhage abates
A “pack and go” technique is used to control bleeding. The fascia is left open, and the skin is closed with towel clips over the tight pelvic pack. Sally is sent to the ICU, where clotting parameters are corrected.
She undergoes reoperation 36 hours later, at which time no bleeding is encountered.
The left ureter is reimplanted into the bladder, and she makes a full recovery.
The author has served on the speakers bureau for Wyeth.
Placenta accreta leads to hemorrhage
Sally is a 27-year-old gravida with 1 prior cesarean whose ultrasound imaging is suspicious for “placenta adherent to the bladder.” At 38 weeks, she delivers a viable infant by classical cesarean, at which time the ultrasound finding is confirmed: the placenta is densely adherent.
The placenta is left in situ, no methotrexate is given, and Sally is followed with clotting studies and exams.
Eight weeks later, when her fibrinogen level falls and the prothrombin time and partial thromboplastin time become abnormal, the obstetrician attempts to perform dilatation and evacuation, but massive bleeding ensues. The physician then performs a total abdominal hysterectomy, but bleeding continues from the cuff.
What is the best way to manage the hemorrhage?
After identifying its source, the surgeon should apply pressure to abate the bleeding, using packing if necessary, and repair the affected artery or vein. Fortunately, we have many tools at our disposal, from preventive steps like careful preoperative assessment to the use of hemostatic agents, fibrin glues, hypogastric artery ligation, and specialized pelvic packing techniques. With prompt action and a stepwise approach, this bona fide catastrophe can usually be successfully managed. This article details a 5-step action plan.
If massive bleeding occurs during laparoscopic or vaginal surgery, a laparotomy may be indicated, and intraoperative management would follow the same 5 steps.
STEP 1Like the Boy Scouts, Be Prepared
Although surgeons are acutely aware that drugs such as warfarin and heparin can cause intraoperative bleeding, the patient history and predisposing factors sometimes get short shrift.
Besides asking about the patient’s medications, assess the following:
- Platelets. The primary laboratory test to evaluate potential bleeding is the platelet count. In general, 10,000 to 20,000 platelets are needed for hemostasis. However, 50,000 are needed for any surgery or invasive procedure, such as insertion of a central line.1 I recommend platelet evaluation for patients scheduled for major abdominal surgery.
- History of bleeding. If the patient or her family has a history of bleeding with any surgery, evaluate her for von Willebrand’s disease.
- High alcohol intake warrants preoperative liver function and coagulation studies.
- Some herbal or natural remedies can exacerbate intraoperative hemorrhage through their inhibition of coagulation, especially the agents listed in TABLE 1. They should generally be discontinued 2 to 7 days before surgery.2
- Aspirin and nonsteroidal anti-inflammatory drugs should be discontinued 7 days before anticipated surgery. However, patients may continue aspirin at a daily dose of 81 mg.
- Poor nutrition and obesity predispose the patient to wound complications and intraoperative bleeding. Patients who are severely malnourished can take dietary supplements or receive total parenteral nutrition prior to surgery.
- Intraoperative factors such as the 3 “inadequacies” (inadequate incision, retraction, and anesthesia), low core body temperature, severe adhesions (ie, endometriosis), and large vascular tumors also are sometimes associated with bleeding.
TABLE 1
Alternative remedies that may exacerbate bleeding
- 32% to 37% of Americans use these remedies, but only 38% of them tell their doctor
- Stop all alternative remedies 2 to 7 days before surgery
| REMEDY | USED FOR | PERIOPERATIVE RISKS |
|---|---|---|
| Beta-carotene | Vitamin A precursor; often taken as a nutritional supplement | May cause coagulopathy |
| Feverfew | Used to prevent or treat migraine and ease menstrual cramps | May inhibit coagulation |
| Fish oil | Rich in omega-3 fatty acids, recommended for cardiovascular health | Omega-3s inhibit coagulation |
| Garlic | Used to reduce hypertension and high cholesterol | Case reports of unexpected or increased surgical bleeding, prolonged bleeding time, and impaired platelet aggregation |
| Ginkgo | Treatment of dementia, impaired cognition, and memory | Various ginkgolides have platelet-activating-factor antagonist properties; case reports of spontaneous bleeding |
| Ginseng | Widely used as a stimulant, tonic, diuretic, mood elevator, and energy booster | May cause hypertension, cardiovascular instability, coagulopathy, and sedation |
| St. John’s wort | Antidepressant | May cause cardiovascular instability, coagulopathy, and sedation |
| Vitamin E | Antioxidant | May interfere with coagulation |
STEP 2Follow These Basic Principles
Whenever bleeding is encountered in any area of the abdominal cavity, the first step is simple: Apply immediate pressure with a finger or sponge stick. Then obtain exposure and assistance. Exposure usually means extending the incision and using a fixed table retractor.
If the source of bleeding is unknown, apply pressure on the aorta using a hand, weighted speculum, or Conn aortic compressor (Pilling-branded, Teleflex Medical, Limerick, Pa).
Secure individual vessels with finetipped clamps and small-caliber sutures or clips, and minimize the use of clamps. Never place clamps or sutures blindly, and never use electrocautery for large lacerations.
If you choose to use packs to temporarily control bleeding, insert them carefully to avoid tearing veins, and place pelvic packs (hot or cold) in a stepwise fashion, from sidewall to sidewall. Leave packs in place for at least 15 minutes and remove them sequentially.
Great vessel injuries
The aorta, vena cava, and common iliac vessels are sometimes injured during removal of paraaortic nodes or when the inferior mesenteric vessels are avulsed during retraction of the sigmoid colon. In addition, needle or trocar injuries during operative laparoscopy occur in as many as 4 of every 10,000 procedures.3
Again, the first step in managing great vessel injuries is applying pressure. Then obtain blood components, and, if necessary, consult with a vascular surgeon or gynecologic oncologist.
In general, once the patient is hemodynamically stable, the affected vessel should be compressed proximally and distally. Use Allis or vascular clamps on the torn edges to elevate the lacerated area. My preference is to close these injuries with a running 5-0 or 6-0 nylon or monofilament polypropylene (MFPP) suture on a cardiovascular needle.
Replacing blood and its components
Be aware of the following replacement guidelines for catastrophic intraoperative hemorrhage:
- For every 8 U of red blood cells replaced, give 2 U of fresh frozen plasma.
- If more than 10 U of red blood cells are replaced, give 10 U of platelets, preferably at the end of the procedure.
- With prolonged PTT, give fresh frozen plasma.
- If fibrinogen is low, give 2 U of cryoprecipitate.1
When massive bleeding is anticipated or encountered, the Haemonetics Cell Saver (Haemonetics Corp, Braintree, Mass) is invaluable. This device, which requires a trained technician, removes blood from the operative field, anticoagulates it, and washes red blood cells, which are infused. It is accepted by many Jehovah’s Witnesses,4 and has been used safely in women with cesarean-associated bleeding.5 Relative contraindications include malignancy and bacterial contamination from a ruptured abscess or inadvertent injury to unprepared bowel.6 The Cell Saver may be used after heavy bleeding from hysterectomy or in patients with ruptured membranes.
STEP 3Try A Topical Hemostatic Agent
If hemorrhage contiues after arterial bleeders are secured, consider a topical hemostatic agent (TABLE 2). All such agents require pressure to be applied for 3 to 5 minutes.
My preferences are Surgicel (Johnson & Johnson, New Brunswick, NJ) and Gelfoam (Pharmacia, Kalamazoo, Mich). In general, Avitene Ultrafoam collagen hemostat (Davol, subsidiary of C.R. Bard, Murray Hill, NJ) works poorly in the presence of thrombocytopenia and should be used with caution near the ureter.
Fibrin glue has been widely used as a hemostatic agent in microvascular, cardiovascular, and thoracic surgery.
To prepare fibrin glue at my institution, we use a double-barrel syringe to apply equal amounts of cryoprecipitate and thrombin at the same time. One fibrin sealant, Tisseal VH (Baxter Healthcare, Deerfield, Ill), comes with a Duploject applicator. After the agent is thoroughly applied (it is sprayed), pressure is applied for 3 to 5 minutes.
The same manufacturer also produces Coseal, which is used in vascular reconstruction to achieve additional hemostasis by mechanically sealing off areas of leakage, and Floseal, to help achieve hemostasis when ligatures or clips are impractical.
TABLE 2
Topical intraperitoneal hemostatic agents
| AGENT | WHAT IT IS | HOW IT IS APPLIED |
|---|---|---|
| Avitene Ultrafoam | Absorbable collagen hemostat | Comes in powder; sprinkle on area |
Fibrin glue
| Equal amounts of cryoprecipitate and thrombin | Spray on affected area with double-barrel syringe or device supplied by Baxter Healthcare |
| Gelfoam | Absorbable gelatin sponge | Cut in strips of appropriate size and apply to area |
| Surgicel | Oxidized regenerated cellulose | Cut in strips of appropriate size and apply to area |
STEP 4Hypogastric Artery Ligation
SALLY’S CASE
Bleeding persists
Because of the hemorrhage, a gynecologic oncology consult is obtained and the hypogastric artery is ligated bilaterally, but bleeding continues. During further exploration, the left ureter is found to be ligated. Sally receives 65 U of packed red blood cells, platelets, and fresh frozen plasma. The Cell Saver also is used.
If pelvic oozing persists after application of a topical hemostatic agent, consider hypogastric artery ligation, which controls pelvic hemorrhage in as many as 50% of patients.7,8
STEP 5When All Else Fails: “Pack And Go”
If intraoperative bleeding persists despite hypogastric artery ligation and the other measures, the life-saving modality of choice is a pelvic pack left in place 2 to 3 days. I prefer a fast, simple method: “pack and go” or damage-control technique.10-12
A 2- to 4-inch Kerlix gauze (Kendall Health Care Products, Mansfield, Mass) is tightly packed over a fibrin glue bed from side to side in the pelvis. Only the skin is closed using towel clips or a running suture. The patient is immediately transferred to intensive care, where acidosis, coagulopathy, and hypothermia are corrected. In 48 to 72 hours, the packs are gently removed with saline drip assistance. If hemostasis still has not been achieved, repacking is an option.
Presacral venous bleeding
Two helpful methods to quell presacral venous bleeding are:
- inserting stainless steel thumbtacks
- indirect coagulation through a muscle fragment
The thumbtack method
The presacral veins are sometimes injured during presacral neurectomy, sacrocolpopexy, or posterior exenteration. This bleeding can be controlled by inserting stainless steel thumbtacks, with direct pressure from the surgeon’s hand, directly into the sacrum.15-17 These work by compressing veins adjacent to the bone, and are left in place permanently. No complications have been reported.
Indirect coagulation
Another method of controlling presacral venous bleeding is indirect coagulation through a muscle fragment. This is done by harvesting a 2 x 1 cm piece of muscle from the rectus abdominus and pressing it against the bleeding veins. Then set a Bovie (Valley Lab, Boulder, Colo) at 40 W of pure cutting current and apply it to the muscle fragment for 1 to 2 minutes. This method has been successful in 12 of 12 reported cases.18,19
Other methods of controlling presacral venous bleeding include bipolar cautery, use of bone wax, and suturing in “sandwiches” of Avitene alternated with Gelfoam, but these strategies have met with limited success.
Pelvic hemorrhage
Arterial embolization
Angiographic insertion of Gelfoam pledgets or Silastic coils may effectively control pelvic hemorrhage in up to 90% of postpartum and postoperative patients.20,21 Hypogastric artery embolization can also be done intraoperatively.22
However, this technique should be used with caution, as it may require 1 to 2 hours to perform and is inappropriate for patients with hypovolemic shock. Complications are rare, but can occur in up to 6% to 7% of patients.21 They include postoperative fever, pelvic abscess formation, reflux of embolic material, nontarget embolization, foot and buttocks ischemia, bladder and rectal wall necrosis, and late rebleeding.
Arterial embolization does not appear to affect subsequent pregnancies.23
Military antishock trousers The MAST or aviation “G” suit is sometimes used as an intermediate step to laparotomy in patients with ectopic pregnancy or postoperative or postpartum hemorrhage.24 Its major use is to stabilize patients for surgery by compressing peripheral circulation, thereby diverting blood to the core circulation.
Inflate the legs first, then the abdomen; leave the MAST suit in place for 2 to 48 hours; and deflate in reverse order.
Contraindications include pulmonary edema, cardiogenic shock, rupture of the diaphragm, and pregnancy.
SALLY’S CASE
Hemorrhage abates
A “pack and go” technique is used to control bleeding. The fascia is left open, and the skin is closed with towel clips over the tight pelvic pack. Sally is sent to the ICU, where clotting parameters are corrected.
She undergoes reoperation 36 hours later, at which time no bleeding is encountered.
The left ureter is reimplanted into the bladder, and she makes a full recovery.
The author has served on the speakers bureau for Wyeth.
1. Nolan TE, Gallup DG. Massive transfusion: a current review. Obstet Gynecol Surv. 1991;46:289-295
2. Ang-Lee MK, Moss J, Yuan C-S. Herbal medicine and preoperative care. JAMA. 2001;286:208-216.
3. Härkü-Siren P, Sjöberg J, Kurki T. Major complications of laparoscopy: a follow-up Finnish study. Obstet Gynecol. 1999;94:94-98.
4. deCastro RM. Bloodless surgery: establishment of a program for the special needs of the Jehovah’s Witness community: the gynecologic surgery experience at a community hospital. Obstet Gynecol. 1999;180:149-158.
5. Rebarber A, Lonser R, Jackson S, Copel JA, Siple S. The safety of intraoperative blood collection and autotransfusion during cesarean section. Am J Obstet Gynecol. 1998;169:715-720.
6. Klimberg I, Sirois R, Wajsman Z, Baker J. Intraoperative autotransfusion in urologic oncology Arch Surg. 1986;121:1326-1329.
7. Clark SL, Phelan JP, Yeh Z-Y, Bruce SR, Paul RH. Hypogastric artery ligation for obstetric hemorrhage. Obstet Gynecol. 1985;66:353-356.
8. Thavarash AS, Sivalingam N, Almohdzar SA. Internal iliac and ovarian artery ligation in the control of pelvic hemorrhage. Aust N Z J Obstet Gynecol. 1989;29:22-25.
9. Burchell RC. Internal iliac ligation. Haemodynamics. Obstet Gynecol. 1964;5:53-59.
10. Finan MA, Fiorica JV, Hoffman MS, et al. Massive pelvic hemorrhage during gynecologic cancer surgery: “pack and go back.” Gynecol Oncol. 1996;62:390-395.
11. Rotondo MF, Zonies DH. The damage control sequence and underlying logic. Surg Clin N Am. 1997;77:761-777.
12. Inge JA, Gallup DG, Davis FE. Catastrophic hemorrhage from placenta previa-accreta. A case series and guidelines for management. J Pelvic Surg. 2000;6:268-272.
13. Cassels JW Jr, Greenberg H, Otterson WN. Pelvic tamponade in puerperal hemorrhage. J Reprod Med. 1985;30:689-692.
14. Hallack M, Didly GA, III, Hurley TJ, Moise KJ, Jr. Transvaginal pressure pack for life-threatening pelvis hemorrhage secondary to placenta accreta. Obstet Gynecol. 1991;78:938-940.
15. Khan FA, Fang DT, Nivatvongs S. Management of presacral hemorrhage during rectal resection. Surg Gynecol Obstet. 1987;165:275-277.
16. Pastner B, Orr JW. Intractable venous hemorrhage: use of stainless steel thumbtacks to obtain hemostasis. Am J Obstet Gynecol. 1990;162:452-455.
17. Timmons MC, Kohler MF, Addison WA. Thumbtack use for control of presacral bleeding with description of an instrument for thumbtack application. Obstet Gynecol. 1991;78:313-315.
18. Xu J, Lin J. Control of presacral hemorrhage with electrocautery through a muscle fragment pressed on the bleeding vein. J Am Coll Surg. 1994;179:351-354.
19. Miklos JR, Kohli N, Sze EH. Control of presacral hemorrhage using indirect coagulation through a muscle fragment. J Pelvic Surg. 1996;2:268-270.
20. Hansch E, Chitkara U, McAlpine J, El-Sayed Y, Dake MD, Razavi MK. Pelvic arterial embolization for control of obstetric hemorrhage: a five-year experience. Obstet Gynecol. 1999;180:1454-1460.
21. Verdantham S, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization: an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol. 1997;176:938-946.
22. Saueracker AJ, McCroskey BL, Moor EE, Moore FA. Intraoperative hypogastric artery embolization for life-threatening pelvic hemorrhage: a preliminary report. J Trauma. 1987;27:1127-1129.
23. Orman D, White R, Pollak J, Tal M. Pelvic embolization for intractable postpartum hemorrhage: long-term follow-up and implications for fertility. Obstet Gynecol. 2003;102:904-910.
24. Pearse CS, Magrina JF, Finley BE. Use of MAST suit in obstetrics and gynecology. Obstet Gynecol Surv. 1984;39:416-422.
1. Nolan TE, Gallup DG. Massive transfusion: a current review. Obstet Gynecol Surv. 1991;46:289-295
2. Ang-Lee MK, Moss J, Yuan C-S. Herbal medicine and preoperative care. JAMA. 2001;286:208-216.
3. Härkü-Siren P, Sjöberg J, Kurki T. Major complications of laparoscopy: a follow-up Finnish study. Obstet Gynecol. 1999;94:94-98.
4. deCastro RM. Bloodless surgery: establishment of a program for the special needs of the Jehovah’s Witness community: the gynecologic surgery experience at a community hospital. Obstet Gynecol. 1999;180:149-158.
5. Rebarber A, Lonser R, Jackson S, Copel JA, Siple S. The safety of intraoperative blood collection and autotransfusion during cesarean section. Am J Obstet Gynecol. 1998;169:715-720.
6. Klimberg I, Sirois R, Wajsman Z, Baker J. Intraoperative autotransfusion in urologic oncology Arch Surg. 1986;121:1326-1329.
7. Clark SL, Phelan JP, Yeh Z-Y, Bruce SR, Paul RH. Hypogastric artery ligation for obstetric hemorrhage. Obstet Gynecol. 1985;66:353-356.
8. Thavarash AS, Sivalingam N, Almohdzar SA. Internal iliac and ovarian artery ligation in the control of pelvic hemorrhage. Aust N Z J Obstet Gynecol. 1989;29:22-25.
9. Burchell RC. Internal iliac ligation. Haemodynamics. Obstet Gynecol. 1964;5:53-59.
10. Finan MA, Fiorica JV, Hoffman MS, et al. Massive pelvic hemorrhage during gynecologic cancer surgery: “pack and go back.” Gynecol Oncol. 1996;62:390-395.
11. Rotondo MF, Zonies DH. The damage control sequence and underlying logic. Surg Clin N Am. 1997;77:761-777.
12. Inge JA, Gallup DG, Davis FE. Catastrophic hemorrhage from placenta previa-accreta. A case series and guidelines for management. J Pelvic Surg. 2000;6:268-272.
13. Cassels JW Jr, Greenberg H, Otterson WN. Pelvic tamponade in puerperal hemorrhage. J Reprod Med. 1985;30:689-692.
14. Hallack M, Didly GA, III, Hurley TJ, Moise KJ, Jr. Transvaginal pressure pack for life-threatening pelvis hemorrhage secondary to placenta accreta. Obstet Gynecol. 1991;78:938-940.
15. Khan FA, Fang DT, Nivatvongs S. Management of presacral hemorrhage during rectal resection. Surg Gynecol Obstet. 1987;165:275-277.
16. Pastner B, Orr JW. Intractable venous hemorrhage: use of stainless steel thumbtacks to obtain hemostasis. Am J Obstet Gynecol. 1990;162:452-455.
17. Timmons MC, Kohler MF, Addison WA. Thumbtack use for control of presacral bleeding with description of an instrument for thumbtack application. Obstet Gynecol. 1991;78:313-315.
18. Xu J, Lin J. Control of presacral hemorrhage with electrocautery through a muscle fragment pressed on the bleeding vein. J Am Coll Surg. 1994;179:351-354.
19. Miklos JR, Kohli N, Sze EH. Control of presacral hemorrhage using indirect coagulation through a muscle fragment. J Pelvic Surg. 1996;2:268-270.
20. Hansch E, Chitkara U, McAlpine J, El-Sayed Y, Dake MD, Razavi MK. Pelvic arterial embolization for control of obstetric hemorrhage: a five-year experience. Obstet Gynecol. 1999;180:1454-1460.
21. Verdantham S, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization: an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol. 1997;176:938-946.
22. Saueracker AJ, McCroskey BL, Moor EE, Moore FA. Intraoperative hypogastric artery embolization for life-threatening pelvic hemorrhage: a preliminary report. J Trauma. 1987;27:1127-1129.
23. Orman D, White R, Pollak J, Tal M. Pelvic embolization for intractable postpartum hemorrhage: long-term follow-up and implications for fertility. Obstet Gynecol. 2003;102:904-910.
24. Pearse CS, Magrina JF, Finley BE. Use of MAST suit in obstetrics and gynecology. Obstet Gynecol Surv. 1984;39:416-422.