User login
Injury-free vaginal surgery: Case-based protective tactics
CASE 1 Gush of fluid during dissection
A 55-year-old woman with 2 prior cesarean deliveries and stage III uterovaginal prolapse (primarily apical) is now undergoing transvaginal hysterectomy and prolapse repair. During sharp dissection of the bladder off the lower uterine segment, a gush of clear fluid washes over the area of dissection.
What steps would you take to achieve the best possible clinical outcome for this woman?
If a patient sustains a urinary tract injury, she is 91 times more likely to sue her surgeon than a patient who has a different complication or problem at gynecologic surgery.1 Yet, despite a surgeon’s best efforts, injury can occur. If it does, the best approach is immediate recognition and repair.
Primary prevention—including identifying the ureters—and intraoperative repair is the easiest, most successful, least morbid approach, compared to postoperative management. And probably less likely to lead to a lawsuit.2
As always, our main goal in any preventive effort is the best possible patient care and clinical outcomes, and diligent, careful surgical technique is the best protection on all counts. Every vaginal surgeon should have a consistent strategy for preventing, indentifying and managing intraoperative injuries to the urinary tract and bowel.
This article discusses potential injuries to the lower genitourinary and gastrointestinal tracts separately.
Vulnerable anatomy is a given
The ureters are injured in up to 2.4% of vaginal surgeries,4 and gynecologic surgery accounts for as much as 52% of inadvertent ureteral injuries.5 The bladder and bowel can also sustain injuries, in up to 2.9% and 8% of cases, respectively.3,6
Mechanisms of injury can include bladder perforation7 (and, rarely, small bowel perforation8) during placement of bladder neck and midurethral slings, transection of the bladder or ureter during vaginal hysterectomy, and ureteral kinking or obstruction during vaginal hysterectomy and vault suspension.4,9
The rectum can sometimes be perforated during posterior colporrhaphy or perineorrhaphy.6
Risk factors
For intraoperative bladder injury: prior anterior colporrhaphy, cesarean delivery, or incontinence surgery.
For injury to the rectum: prior posterior vaginal wall surgery and defects in the distal rectovaginal septum.
For injury to the small bowel: enterocele.
Women with surgically induced or suspected congenital anatomic anomalies (eg, ureteral reimplantation, ectopic kidneys or ureters, suprapubic vascular bypass grafts) require evaluation to establish the location of these anatomic variants with respect to the planned area of surgical exploration.
Most gyn surgical injuries involve the urinary tract
The urethra and a substantial portion of the posterior bladder rest on and are supported by the anterior vaginal wall. In women with an intact uterus, the posterior bladder wall also rests on the anterior lower uterine segment.
In women with a uterine scar, the bladder wall itself can sometimes be scarred down to the anterior lower uterine segment. This scarring occurs when the lower uterine scar becomes adherent to the posterior bladder wall during wound healing. Unrepaired or delayed repair to bladder injuries in these areas may lead to fistula formation.
Prior anterior colporrhaphy is associated with scarring between the bladder and anterior vaginal walls and can increase the risk of bladder injury during vaginal surgery.
Intraoperative injuries to the bladder dome and bladder neck are most common during urethral and bladder-neck sling procedures. During these procedures, prevent injury by keeping the passing tip of the sling-insertion device (eg, trocar or other passing instrument) clear of the urethra and bladder neck, and perform cystourethroscopy during each pass to identify any perforation of the bladder or urethra.
When perforation occurs, inspect the ureteral orifices thoroughly and document prompt efflux from both. If the orifices are freely effluxing and the remainder of the bladder mucosa is intact, withdraw the perforating instrument, pass it through again, and repeat cystoscopy to confirm that there is no new perforation.
Perforations to the bladder dome usually heal spontaneously in the postoperative period, with no need for extended bladder drainage. Perforations at the lateral or anterior bladder neck will also heal spontaneously.
Injuries to the posterior bladder wall and trigone
These injuries can occur during vaginal hysterectomy or dissection of the anterior vaginal wall (eg, anterior colporrhaphy, paravaginal defect repair). Avoid injuries by dissecting the vaginal mucosa (and lower uterine segment) carefully off the underlying endopelvic tissues.
Signs of an injury
Injury is often heralded by a gush of urine into the vaginal operative field, as in the opening case. When it occurs, determine the extent of injury from the vaginal side, and use a small Allis clamp to temporarily close the injury so that cystourethroscopy is effective. During cystoscopy, take steps to ascertain the extent of the injury and its proximity to the ureteral orifices.
Vaginal approach to intraoperative repair
Lacerations 2 cm or less in size are usually amenable to vaginal repair. In general, if the full extent of the laceration can be visually appreciated and accessed using the vaginal route, the repair can be safely attempted from the vaginal approach.
If the perforation is well away (>1 cm) from the ureteral orifices and there is free efflux from both orifices, close the defect from the vaginal side in 3 imbricating layers, being careful to keep the suture knots out of the bladder lumen.
Start by dissecting the overlying vaginal mucosa off the endopelvic fascia for 1 cm around the defect. This exposes the bladder adventitia, which can be used to reapproximate the laceration as follows:
Test the repair
Backfill the bladder transurethrally with 100 cc of sterile infant formula, and observe the result on the vaginal side. Closure should be watertight. Sterile formula does not stain the tissues and is therefore preferable to indigo carmine or methylene blue.
Reapproximate the vaginal mucosa using 2-0 Monocryl suture in a running, “nonlocked” fashion. Repeat cystoscopy after the closure to ensure prompt, free efflux from both ureteral orifices.
In nonradiated, well-perfused tissues, an interposing fat pad (eg, Martius or omental) is usually not required.
Foley catheter drainage is recommended to allow about 3 weeks of healing time for the closure.
If the laceration is less than 1 cm from a ureteral orifice
Assess the integrity of the affected ureter using a retrograde ureterogram performed under fluoroscopy. If ureteral integrity is confirmed, the affected ureter may be stented prior to repair of the laceration (as discussed above). Any stents may be left in place until the repair is judged to be sufficiently healed.
If the laceration is not fully visible or accessible vaginally
Use an abdominal approach—either open or laparoscopic—after assessing ureteral integrity. Focus on developing a suitable plane between the bladder and vaginal walls around the defect, followed by reapproximation of the bladder in 3 imbricating running layers of absorbable monofilament suture, as described above.
If the injury occurs during vaginal hysterectomy
In this situation, bladder closure can be deferred until the uterus and ovaries (if planned) have been removed.
For other procedures, such as anterior colporrhaphy, finish the procedure after the bladder is successfully closed. If the perforation is near or involves either ureteral orifice, it should be addressed in the manner of a ureteral injury (see below).
After fistula repairs
My patients undergo fluoroscopic evaluation of bladder filling and emptying at the 3-week mark, prior to Foley removal, to document functional closure. Then the Foley catheter and any indwelling stents are removed.
I counsel patients about the need to empty the bladder frequently, and how to recognize and avoid urinary retention.
Injuries to the ureters
The pelvic aspect of the ureters is also of interest to the gynecologic surgeon because these structures are at risk for obstruction or transection.
Vaginal procedures that can put the ureters at risk include vaginal vault (apical) suspensions and paravaginal defect repairs. Always include cystourethroscopy at the end of these procedures to document prompt and free efflux from both ureteral orifices.
3 “risky” regions
Because of its proximity to the vagina and uterus, the bladder is sometimes injured during vaginal surgery. Three areas are vulnerable: the dome and bladder neck/urethra, at risk during sling procedures, and the posterior bladder wall, vulnerable during dissection of the anterior vaginal wall.
If cystoscopy fails to confirm definitive bilateral efflux
Infuse intravenous indigo carmine and inspect the ureteral orifices again, in this situation. If bilateral efflux is not forthcoming, consider removing any intrapelvic packing, and take the patient out of the Trendelenburg position so that she can be observed for 20 minutes.
If there is still no efflux after that interval, a ureter may be obstructed.
If you suspect ureteral kinking or obstruction
Consider removing any suspensory sutures near the obstructed (noneffluxing) ureter. This maneuver usually results in vigorous efflux from the affected orifice.10 In the case of apical suspension sutures, remove the most lateral suture first and perform cystoscopy after each (more medial) suture is removed.4,9
If suture removal fails to bring about ureteral efflux, evaluate the ureters further by using intraoperative retrograde ureterogram (pyelogram) under fluoroscopy or by placing ureteral stents under cystoscopic guidance. Either method will localize the obstruction or kink and allow for targeted exploration and release of the stricture.
Extended bladder drainage is usually not required after intraoperative release of a partially or completely obstructed ureter.
In my practice, I remove any permanent suture I suspect is kinking or partially kinking a ureter. If the suture causing the problem is an absorbable one (eg, as in the use of Vicryl suture at colpocleisis), I may choose to follow the patient or to place a stent, and I reassure the woman that the offending suture will dissolve over time, thus relieving the partial obstruction.
If blue dye enters the field from inside the pelvis
The problem may be partial or complete ureteral transection. In this case, bladder perforation must first be ruled out cystoscopically. Then perform retrograde ureterogram under fluoroscopy to look for the possible point of leakage.
If ureteral transection is confirmed, plan for thorough surgical exploration (usually via the abdominal route) to locate and repair the injury.
For many generalists, this may require an intraoperative consult from a surgical service comfortable with the repair and/or reimplantation of the ureters.
CASE 1 OUTCOME
The bladder laceration was repaired after completion of the vaginal hysterectomy in the manner described above. There were no further sequelae.
It pays to refamiliarize yourself with the particular “landscape” of the lower urinary tract, so that sutures or scalpels don’t inadvertently block or injure structures.
The smooth muscle of the bladder (detrusor) is lined with transitional mucosal epithelium and opens into the urethra at the bladder neck.
The ureters enter into the lateral aspects of the midposterior bladder and tunnel medially through the detrusor muscle before entering the bladder lumen at the level of the interureteral ridge. These entry points are known as the ureteral orifices.
The trigone is an area of the posterior bladder wall bounded by the bladder neck inferiorly and by the 2 ureteral orifices in the posterior midbladder.
Rectal injuries are usually easy to identify
As far as vaginal surgery is concerned, the lower GI tract consists of the rectum and external and internal anal sphincters. The distal rectum and posterior vaginal wall are usually closely applied to each other, separated by the rectovaginal septum (also called Denonvilliers fascia).
Risk factors
In women who have undergone posterior colporrhaphy or repair of a 4th degree tear, the posterior vaginal wall can be densely adherent to the rectum, putting the rectum at risk for injury during posterior vaginal wall dissection.
Most injuries to the rectum occur during dissection of the posterior vaginal wall. Fortunately, these injuries are readily recognized and easily repaired. If a rectal injury is suspected during or after dissection, a thorough intraoperative digital exam will help confirm or rule it out.
Repair of a rectal injury
Once an injury is identified, reapproximate the rectal mucosal edges with an imbricating closure using 3-0 Monocryl or other absorbable monofilament suture. A second imbricating layer should bring the rectal muscularis together, and the rectovaginal septum can then be closed over this layer in side-to-side or transverse fashion. Finally, close the vaginal mucosa after appropriate posterior colporrhaphy trimming. Such repairs heal well over time, without any long-term effects for the patient.
Prescribe a stool softener for the first 3 postoperative months to reduce the patient’s need to strain.
No bowel prep needed because injuries are rare
In my practice, the vast majority of vaginal surgical cases are accomplished without the need for preoperative bowel preparation. In the occasional patient known to have dense small-bowel adhesions involving the uterus, adnexae, or vaginal cuff, bowel prep may be appropriate if substantial dissection of the bowel is anticipated as part of the procedure.
CASE 2 Small bowel laceration
A 45-year-old woman with 4 prior vaginal deliveries, a 4th-degree obstetric rectovaginal laceration, and a history of laparoscopically assisted vaginal hysterectomy presents with stage III pelvic organ prolapse, primarily involving the posterior vaginal wall. An examination reveals a defect in the upper aspect of the posterior wall (an apical defect).
Intraoperatively, during sharp dissection to lift the posterior vaginal wall off the rectovaginal septum, a loop of small bowel descends into the field, and a 1-cm laceration occurs, exposing the lumen of the bowel.
How do you proceed?
On very rare occasions, a patient with an enterocele may sustain a small bowel injury during vaginal surgery. Such injury can usually be avoided by packing the small bowel away from the area of dissection and closely observing the dissection field.
Transvaginal repair
If the small bowel is cut during dissection, inspect the adjacent small bowel thoroughly to ascertain the extent of the injury. Transvaginal repair is recommended if the laceration and adjacent mesentery can be completely visualized and accessed through the vagina.
Small lacerations require a simple closure
If the laceration is small (1–2 cm) and does not involve the mesentery, irrigate it thoroughly and close it using a running imbricating 2-0 braided suture (eg, Vicryl or silk), with the suture line perpendicular to the long axis of the small bowel to decrease the risk of stricture. Inspect the suture line to ensure that it completely seals the laceration. Suture bites should incorporate the serosa and muscularis without transgressing the mucosa. Use a noncutting needle to place these sutures.
If the mesentery is involved in the laceration, make sure there are no bleeding vessels, and ligate any bleeding ones.
Large lacerations may necessitate abdominal surgery
An abdominal or laparoscopic procedure may be necessary to repair larger lacerations to the small bowel. If the surgeon is uncomfortable with bowel repair, it may be appropriate to obtain an intraoperative consult from a surgical service.
Postoperative monitoring
Watch for signs of ileus, which should be managed with bowel rest and nasogastric suction, as indicated.
CASE 2 OUTCOME
The small laceration was repaired with 2-0 Vicryl suture in the manner described above. The patient’s diet was advanced when bowel sounds returned. There were no further sequelae.
Generalists can manage most injuries
Incidental intraoperative injuries to the lower urinary and gastrointestinal tracts are relatively rare complications of vaginal surgery—but we must make every effort to anticipate, prevent, and promptly recognize such injuries.
If they do occur, pursue a course to thoroughly evaluate, repair, test, and provide appropriate followup for the patient. If promptly identified and addressed, these injuries can be made to resolve with minimal long-term sequelae. Appropriately timed intraoperative cystoscopy is a useful method for prompt intraoperative identification of bladder and ureteric injuries. Injuries identified intraoperatively can usually be repaired using simple techniques available to the general gynecologist.
The author reports no financial relationships relevant to this article
1. Gilmour DT, Baskett TF. Disability and litigation from urinary tract injuries at benign gynecologic surgery in Canada. Obstet Gynecol. 2005;105:109-114.
2. Pettit PD, Petrou SP. The value of cystoscopy in major vaginal surgery. Obstet Gynecol. 1994;84:318-320.
3. Gilmour DT, Dwyer PL, Carey MP. Lower urinary tract injury during gynecologic surgery and its detection by intraoperative cystoscopy. Obstet Gynecol. 1999;94:883-889.
4. Karram M, Goldwasser S, Kleeman S, et al. High uterosacral vaginal vault suspension with fascial reconstruction for vaginal repair of enterocele and vaginal vault prolapse. Am J Obstet Gynecol. 2001;185:1339-1342discussion 1342-1343.
5. Dowling RA, Corriere JN, Jr, Sandler CM. Iatrogenic ureteral injury. J Urol. 1986;135:912-915.
6. Mercer-Jones MA, Sprowson A, Varma JS. Outcome after transperineal mesh repair of rectocele: a case series. Dis Colon Rectum. 2004;47:864-868.
7. McLennan MT, Melick CF. Bladder perforation during tension-free vaginal tape procedures: analysis of learning curve and risk factors. Obstet Gynecol. 2005;106:1000-1004.
8. Leboeuf L, Tellez CA, Ead D, Gousse AE. Complication of bowel perforation during insertion of tension-free vaginal tape. J Urol. 2003;170:1310-discussion 1310-1311.
9. Shull BL, Bachofen C, Coates KW, Kuehl TJ. A transvaginal approach to repair of apical and other associated sites of pelvic organ prolapse with uterosacral ligaments. Am J Obstet Gynecol. 2000;183:1365-1373discussion 1373-1374.
10. Harris RL, Cundiff GW, Theofrastous JP, et al. The value of intraoperative cystoscopy in urogynecologic and reconstructive pelvic surgery. Am J Obstet Gynecol. 1997;177:1367-1369discussion 1369-1371.
CASE 1 Gush of fluid during dissection
A 55-year-old woman with 2 prior cesarean deliveries and stage III uterovaginal prolapse (primarily apical) is now undergoing transvaginal hysterectomy and prolapse repair. During sharp dissection of the bladder off the lower uterine segment, a gush of clear fluid washes over the area of dissection.
What steps would you take to achieve the best possible clinical outcome for this woman?
If a patient sustains a urinary tract injury, she is 91 times more likely to sue her surgeon than a patient who has a different complication or problem at gynecologic surgery.1 Yet, despite a surgeon’s best efforts, injury can occur. If it does, the best approach is immediate recognition and repair.
Primary prevention—including identifying the ureters—and intraoperative repair is the easiest, most successful, least morbid approach, compared to postoperative management. And probably less likely to lead to a lawsuit.2
As always, our main goal in any preventive effort is the best possible patient care and clinical outcomes, and diligent, careful surgical technique is the best protection on all counts. Every vaginal surgeon should have a consistent strategy for preventing, indentifying and managing intraoperative injuries to the urinary tract and bowel.
This article discusses potential injuries to the lower genitourinary and gastrointestinal tracts separately.
Vulnerable anatomy is a given
The ureters are injured in up to 2.4% of vaginal surgeries,4 and gynecologic surgery accounts for as much as 52% of inadvertent ureteral injuries.5 The bladder and bowel can also sustain injuries, in up to 2.9% and 8% of cases, respectively.3,6
Mechanisms of injury can include bladder perforation7 (and, rarely, small bowel perforation8) during placement of bladder neck and midurethral slings, transection of the bladder or ureter during vaginal hysterectomy, and ureteral kinking or obstruction during vaginal hysterectomy and vault suspension.4,9
The rectum can sometimes be perforated during posterior colporrhaphy or perineorrhaphy.6
Risk factors
For intraoperative bladder injury: prior anterior colporrhaphy, cesarean delivery, or incontinence surgery.
For injury to the rectum: prior posterior vaginal wall surgery and defects in the distal rectovaginal septum.
For injury to the small bowel: enterocele.
Women with surgically induced or suspected congenital anatomic anomalies (eg, ureteral reimplantation, ectopic kidneys or ureters, suprapubic vascular bypass grafts) require evaluation to establish the location of these anatomic variants with respect to the planned area of surgical exploration.
Most gyn surgical injuries involve the urinary tract
The urethra and a substantial portion of the posterior bladder rest on and are supported by the anterior vaginal wall. In women with an intact uterus, the posterior bladder wall also rests on the anterior lower uterine segment.
In women with a uterine scar, the bladder wall itself can sometimes be scarred down to the anterior lower uterine segment. This scarring occurs when the lower uterine scar becomes adherent to the posterior bladder wall during wound healing. Unrepaired or delayed repair to bladder injuries in these areas may lead to fistula formation.
Prior anterior colporrhaphy is associated with scarring between the bladder and anterior vaginal walls and can increase the risk of bladder injury during vaginal surgery.
Intraoperative injuries to the bladder dome and bladder neck are most common during urethral and bladder-neck sling procedures. During these procedures, prevent injury by keeping the passing tip of the sling-insertion device (eg, trocar or other passing instrument) clear of the urethra and bladder neck, and perform cystourethroscopy during each pass to identify any perforation of the bladder or urethra.
When perforation occurs, inspect the ureteral orifices thoroughly and document prompt efflux from both. If the orifices are freely effluxing and the remainder of the bladder mucosa is intact, withdraw the perforating instrument, pass it through again, and repeat cystoscopy to confirm that there is no new perforation.
Perforations to the bladder dome usually heal spontaneously in the postoperative period, with no need for extended bladder drainage. Perforations at the lateral or anterior bladder neck will also heal spontaneously.
Injuries to the posterior bladder wall and trigone
These injuries can occur during vaginal hysterectomy or dissection of the anterior vaginal wall (eg, anterior colporrhaphy, paravaginal defect repair). Avoid injuries by dissecting the vaginal mucosa (and lower uterine segment) carefully off the underlying endopelvic tissues.
Signs of an injury
Injury is often heralded by a gush of urine into the vaginal operative field, as in the opening case. When it occurs, determine the extent of injury from the vaginal side, and use a small Allis clamp to temporarily close the injury so that cystourethroscopy is effective. During cystoscopy, take steps to ascertain the extent of the injury and its proximity to the ureteral orifices.
Vaginal approach to intraoperative repair
Lacerations 2 cm or less in size are usually amenable to vaginal repair. In general, if the full extent of the laceration can be visually appreciated and accessed using the vaginal route, the repair can be safely attempted from the vaginal approach.
If the perforation is well away (>1 cm) from the ureteral orifices and there is free efflux from both orifices, close the defect from the vaginal side in 3 imbricating layers, being careful to keep the suture knots out of the bladder lumen.
Start by dissecting the overlying vaginal mucosa off the endopelvic fascia for 1 cm around the defect. This exposes the bladder adventitia, which can be used to reapproximate the laceration as follows:
Test the repair
Backfill the bladder transurethrally with 100 cc of sterile infant formula, and observe the result on the vaginal side. Closure should be watertight. Sterile formula does not stain the tissues and is therefore preferable to indigo carmine or methylene blue.
Reapproximate the vaginal mucosa using 2-0 Monocryl suture in a running, “nonlocked” fashion. Repeat cystoscopy after the closure to ensure prompt, free efflux from both ureteral orifices.
In nonradiated, well-perfused tissues, an interposing fat pad (eg, Martius or omental) is usually not required.
Foley catheter drainage is recommended to allow about 3 weeks of healing time for the closure.
If the laceration is less than 1 cm from a ureteral orifice
Assess the integrity of the affected ureter using a retrograde ureterogram performed under fluoroscopy. If ureteral integrity is confirmed, the affected ureter may be stented prior to repair of the laceration (as discussed above). Any stents may be left in place until the repair is judged to be sufficiently healed.
If the laceration is not fully visible or accessible vaginally
Use an abdominal approach—either open or laparoscopic—after assessing ureteral integrity. Focus on developing a suitable plane between the bladder and vaginal walls around the defect, followed by reapproximation of the bladder in 3 imbricating running layers of absorbable monofilament suture, as described above.
If the injury occurs during vaginal hysterectomy
In this situation, bladder closure can be deferred until the uterus and ovaries (if planned) have been removed.
For other procedures, such as anterior colporrhaphy, finish the procedure after the bladder is successfully closed. If the perforation is near or involves either ureteral orifice, it should be addressed in the manner of a ureteral injury (see below).
After fistula repairs
My patients undergo fluoroscopic evaluation of bladder filling and emptying at the 3-week mark, prior to Foley removal, to document functional closure. Then the Foley catheter and any indwelling stents are removed.
I counsel patients about the need to empty the bladder frequently, and how to recognize and avoid urinary retention.
Injuries to the ureters
The pelvic aspect of the ureters is also of interest to the gynecologic surgeon because these structures are at risk for obstruction or transection.
Vaginal procedures that can put the ureters at risk include vaginal vault (apical) suspensions and paravaginal defect repairs. Always include cystourethroscopy at the end of these procedures to document prompt and free efflux from both ureteral orifices.
3 “risky” regions
Because of its proximity to the vagina and uterus, the bladder is sometimes injured during vaginal surgery. Three areas are vulnerable: the dome and bladder neck/urethra, at risk during sling procedures, and the posterior bladder wall, vulnerable during dissection of the anterior vaginal wall.
If cystoscopy fails to confirm definitive bilateral efflux
Infuse intravenous indigo carmine and inspect the ureteral orifices again, in this situation. If bilateral efflux is not forthcoming, consider removing any intrapelvic packing, and take the patient out of the Trendelenburg position so that she can be observed for 20 minutes.
If there is still no efflux after that interval, a ureter may be obstructed.
If you suspect ureteral kinking or obstruction
Consider removing any suspensory sutures near the obstructed (noneffluxing) ureter. This maneuver usually results in vigorous efflux from the affected orifice.10 In the case of apical suspension sutures, remove the most lateral suture first and perform cystoscopy after each (more medial) suture is removed.4,9
If suture removal fails to bring about ureteral efflux, evaluate the ureters further by using intraoperative retrograde ureterogram (pyelogram) under fluoroscopy or by placing ureteral stents under cystoscopic guidance. Either method will localize the obstruction or kink and allow for targeted exploration and release of the stricture.
Extended bladder drainage is usually not required after intraoperative release of a partially or completely obstructed ureter.
In my practice, I remove any permanent suture I suspect is kinking or partially kinking a ureter. If the suture causing the problem is an absorbable one (eg, as in the use of Vicryl suture at colpocleisis), I may choose to follow the patient or to place a stent, and I reassure the woman that the offending suture will dissolve over time, thus relieving the partial obstruction.
If blue dye enters the field from inside the pelvis
The problem may be partial or complete ureteral transection. In this case, bladder perforation must first be ruled out cystoscopically. Then perform retrograde ureterogram under fluoroscopy to look for the possible point of leakage.
If ureteral transection is confirmed, plan for thorough surgical exploration (usually via the abdominal route) to locate and repair the injury.
For many generalists, this may require an intraoperative consult from a surgical service comfortable with the repair and/or reimplantation of the ureters.
CASE 1 OUTCOME
The bladder laceration was repaired after completion of the vaginal hysterectomy in the manner described above. There were no further sequelae.
It pays to refamiliarize yourself with the particular “landscape” of the lower urinary tract, so that sutures or scalpels don’t inadvertently block or injure structures.
The smooth muscle of the bladder (detrusor) is lined with transitional mucosal epithelium and opens into the urethra at the bladder neck.
The ureters enter into the lateral aspects of the midposterior bladder and tunnel medially through the detrusor muscle before entering the bladder lumen at the level of the interureteral ridge. These entry points are known as the ureteral orifices.
The trigone is an area of the posterior bladder wall bounded by the bladder neck inferiorly and by the 2 ureteral orifices in the posterior midbladder.
Rectal injuries are usually easy to identify
As far as vaginal surgery is concerned, the lower GI tract consists of the rectum and external and internal anal sphincters. The distal rectum and posterior vaginal wall are usually closely applied to each other, separated by the rectovaginal septum (also called Denonvilliers fascia).
Risk factors
In women who have undergone posterior colporrhaphy or repair of a 4th degree tear, the posterior vaginal wall can be densely adherent to the rectum, putting the rectum at risk for injury during posterior vaginal wall dissection.
Most injuries to the rectum occur during dissection of the posterior vaginal wall. Fortunately, these injuries are readily recognized and easily repaired. If a rectal injury is suspected during or after dissection, a thorough intraoperative digital exam will help confirm or rule it out.
Repair of a rectal injury
Once an injury is identified, reapproximate the rectal mucosal edges with an imbricating closure using 3-0 Monocryl or other absorbable monofilament suture. A second imbricating layer should bring the rectal muscularis together, and the rectovaginal septum can then be closed over this layer in side-to-side or transverse fashion. Finally, close the vaginal mucosa after appropriate posterior colporrhaphy trimming. Such repairs heal well over time, without any long-term effects for the patient.
Prescribe a stool softener for the first 3 postoperative months to reduce the patient’s need to strain.
No bowel prep needed because injuries are rare
In my practice, the vast majority of vaginal surgical cases are accomplished without the need for preoperative bowel preparation. In the occasional patient known to have dense small-bowel adhesions involving the uterus, adnexae, or vaginal cuff, bowel prep may be appropriate if substantial dissection of the bowel is anticipated as part of the procedure.
CASE 2 Small bowel laceration
A 45-year-old woman with 4 prior vaginal deliveries, a 4th-degree obstetric rectovaginal laceration, and a history of laparoscopically assisted vaginal hysterectomy presents with stage III pelvic organ prolapse, primarily involving the posterior vaginal wall. An examination reveals a defect in the upper aspect of the posterior wall (an apical defect).
Intraoperatively, during sharp dissection to lift the posterior vaginal wall off the rectovaginal septum, a loop of small bowel descends into the field, and a 1-cm laceration occurs, exposing the lumen of the bowel.
How do you proceed?
On very rare occasions, a patient with an enterocele may sustain a small bowel injury during vaginal surgery. Such injury can usually be avoided by packing the small bowel away from the area of dissection and closely observing the dissection field.
Transvaginal repair
If the small bowel is cut during dissection, inspect the adjacent small bowel thoroughly to ascertain the extent of the injury. Transvaginal repair is recommended if the laceration and adjacent mesentery can be completely visualized and accessed through the vagina.
Small lacerations require a simple closure
If the laceration is small (1–2 cm) and does not involve the mesentery, irrigate it thoroughly and close it using a running imbricating 2-0 braided suture (eg, Vicryl or silk), with the suture line perpendicular to the long axis of the small bowel to decrease the risk of stricture. Inspect the suture line to ensure that it completely seals the laceration. Suture bites should incorporate the serosa and muscularis without transgressing the mucosa. Use a noncutting needle to place these sutures.
If the mesentery is involved in the laceration, make sure there are no bleeding vessels, and ligate any bleeding ones.
Large lacerations may necessitate abdominal surgery
An abdominal or laparoscopic procedure may be necessary to repair larger lacerations to the small bowel. If the surgeon is uncomfortable with bowel repair, it may be appropriate to obtain an intraoperative consult from a surgical service.
Postoperative monitoring
Watch for signs of ileus, which should be managed with bowel rest and nasogastric suction, as indicated.
CASE 2 OUTCOME
The small laceration was repaired with 2-0 Vicryl suture in the manner described above. The patient’s diet was advanced when bowel sounds returned. There were no further sequelae.
Generalists can manage most injuries
Incidental intraoperative injuries to the lower urinary and gastrointestinal tracts are relatively rare complications of vaginal surgery—but we must make every effort to anticipate, prevent, and promptly recognize such injuries.
If they do occur, pursue a course to thoroughly evaluate, repair, test, and provide appropriate followup for the patient. If promptly identified and addressed, these injuries can be made to resolve with minimal long-term sequelae. Appropriately timed intraoperative cystoscopy is a useful method for prompt intraoperative identification of bladder and ureteric injuries. Injuries identified intraoperatively can usually be repaired using simple techniques available to the general gynecologist.
The author reports no financial relationships relevant to this article
CASE 1 Gush of fluid during dissection
A 55-year-old woman with 2 prior cesarean deliveries and stage III uterovaginal prolapse (primarily apical) is now undergoing transvaginal hysterectomy and prolapse repair. During sharp dissection of the bladder off the lower uterine segment, a gush of clear fluid washes over the area of dissection.
What steps would you take to achieve the best possible clinical outcome for this woman?
If a patient sustains a urinary tract injury, she is 91 times more likely to sue her surgeon than a patient who has a different complication or problem at gynecologic surgery.1 Yet, despite a surgeon’s best efforts, injury can occur. If it does, the best approach is immediate recognition and repair.
Primary prevention—including identifying the ureters—and intraoperative repair is the easiest, most successful, least morbid approach, compared to postoperative management. And probably less likely to lead to a lawsuit.2
As always, our main goal in any preventive effort is the best possible patient care and clinical outcomes, and diligent, careful surgical technique is the best protection on all counts. Every vaginal surgeon should have a consistent strategy for preventing, indentifying and managing intraoperative injuries to the urinary tract and bowel.
This article discusses potential injuries to the lower genitourinary and gastrointestinal tracts separately.
Vulnerable anatomy is a given
The ureters are injured in up to 2.4% of vaginal surgeries,4 and gynecologic surgery accounts for as much as 52% of inadvertent ureteral injuries.5 The bladder and bowel can also sustain injuries, in up to 2.9% and 8% of cases, respectively.3,6
Mechanisms of injury can include bladder perforation7 (and, rarely, small bowel perforation8) during placement of bladder neck and midurethral slings, transection of the bladder or ureter during vaginal hysterectomy, and ureteral kinking or obstruction during vaginal hysterectomy and vault suspension.4,9
The rectum can sometimes be perforated during posterior colporrhaphy or perineorrhaphy.6
Risk factors
For intraoperative bladder injury: prior anterior colporrhaphy, cesarean delivery, or incontinence surgery.
For injury to the rectum: prior posterior vaginal wall surgery and defects in the distal rectovaginal septum.
For injury to the small bowel: enterocele.
Women with surgically induced or suspected congenital anatomic anomalies (eg, ureteral reimplantation, ectopic kidneys or ureters, suprapubic vascular bypass grafts) require evaluation to establish the location of these anatomic variants with respect to the planned area of surgical exploration.
Most gyn surgical injuries involve the urinary tract
The urethra and a substantial portion of the posterior bladder rest on and are supported by the anterior vaginal wall. In women with an intact uterus, the posterior bladder wall also rests on the anterior lower uterine segment.
In women with a uterine scar, the bladder wall itself can sometimes be scarred down to the anterior lower uterine segment. This scarring occurs when the lower uterine scar becomes adherent to the posterior bladder wall during wound healing. Unrepaired or delayed repair to bladder injuries in these areas may lead to fistula formation.
Prior anterior colporrhaphy is associated with scarring between the bladder and anterior vaginal walls and can increase the risk of bladder injury during vaginal surgery.
Intraoperative injuries to the bladder dome and bladder neck are most common during urethral and bladder-neck sling procedures. During these procedures, prevent injury by keeping the passing tip of the sling-insertion device (eg, trocar or other passing instrument) clear of the urethra and bladder neck, and perform cystourethroscopy during each pass to identify any perforation of the bladder or urethra.
When perforation occurs, inspect the ureteral orifices thoroughly and document prompt efflux from both. If the orifices are freely effluxing and the remainder of the bladder mucosa is intact, withdraw the perforating instrument, pass it through again, and repeat cystoscopy to confirm that there is no new perforation.
Perforations to the bladder dome usually heal spontaneously in the postoperative period, with no need for extended bladder drainage. Perforations at the lateral or anterior bladder neck will also heal spontaneously.
Injuries to the posterior bladder wall and trigone
These injuries can occur during vaginal hysterectomy or dissection of the anterior vaginal wall (eg, anterior colporrhaphy, paravaginal defect repair). Avoid injuries by dissecting the vaginal mucosa (and lower uterine segment) carefully off the underlying endopelvic tissues.
Signs of an injury
Injury is often heralded by a gush of urine into the vaginal operative field, as in the opening case. When it occurs, determine the extent of injury from the vaginal side, and use a small Allis clamp to temporarily close the injury so that cystourethroscopy is effective. During cystoscopy, take steps to ascertain the extent of the injury and its proximity to the ureteral orifices.
Vaginal approach to intraoperative repair
Lacerations 2 cm or less in size are usually amenable to vaginal repair. In general, if the full extent of the laceration can be visually appreciated and accessed using the vaginal route, the repair can be safely attempted from the vaginal approach.
If the perforation is well away (>1 cm) from the ureteral orifices and there is free efflux from both orifices, close the defect from the vaginal side in 3 imbricating layers, being careful to keep the suture knots out of the bladder lumen.
Start by dissecting the overlying vaginal mucosa off the endopelvic fascia for 1 cm around the defect. This exposes the bladder adventitia, which can be used to reapproximate the laceration as follows:
Test the repair
Backfill the bladder transurethrally with 100 cc of sterile infant formula, and observe the result on the vaginal side. Closure should be watertight. Sterile formula does not stain the tissues and is therefore preferable to indigo carmine or methylene blue.
Reapproximate the vaginal mucosa using 2-0 Monocryl suture in a running, “nonlocked” fashion. Repeat cystoscopy after the closure to ensure prompt, free efflux from both ureteral orifices.
In nonradiated, well-perfused tissues, an interposing fat pad (eg, Martius or omental) is usually not required.
Foley catheter drainage is recommended to allow about 3 weeks of healing time for the closure.
If the laceration is less than 1 cm from a ureteral orifice
Assess the integrity of the affected ureter using a retrograde ureterogram performed under fluoroscopy. If ureteral integrity is confirmed, the affected ureter may be stented prior to repair of the laceration (as discussed above). Any stents may be left in place until the repair is judged to be sufficiently healed.
If the laceration is not fully visible or accessible vaginally
Use an abdominal approach—either open or laparoscopic—after assessing ureteral integrity. Focus on developing a suitable plane between the bladder and vaginal walls around the defect, followed by reapproximation of the bladder in 3 imbricating running layers of absorbable monofilament suture, as described above.
If the injury occurs during vaginal hysterectomy
In this situation, bladder closure can be deferred until the uterus and ovaries (if planned) have been removed.
For other procedures, such as anterior colporrhaphy, finish the procedure after the bladder is successfully closed. If the perforation is near or involves either ureteral orifice, it should be addressed in the manner of a ureteral injury (see below).
After fistula repairs
My patients undergo fluoroscopic evaluation of bladder filling and emptying at the 3-week mark, prior to Foley removal, to document functional closure. Then the Foley catheter and any indwelling stents are removed.
I counsel patients about the need to empty the bladder frequently, and how to recognize and avoid urinary retention.
Injuries to the ureters
The pelvic aspect of the ureters is also of interest to the gynecologic surgeon because these structures are at risk for obstruction or transection.
Vaginal procedures that can put the ureters at risk include vaginal vault (apical) suspensions and paravaginal defect repairs. Always include cystourethroscopy at the end of these procedures to document prompt and free efflux from both ureteral orifices.
3 “risky” regions
Because of its proximity to the vagina and uterus, the bladder is sometimes injured during vaginal surgery. Three areas are vulnerable: the dome and bladder neck/urethra, at risk during sling procedures, and the posterior bladder wall, vulnerable during dissection of the anterior vaginal wall.
If cystoscopy fails to confirm definitive bilateral efflux
Infuse intravenous indigo carmine and inspect the ureteral orifices again, in this situation. If bilateral efflux is not forthcoming, consider removing any intrapelvic packing, and take the patient out of the Trendelenburg position so that she can be observed for 20 minutes.
If there is still no efflux after that interval, a ureter may be obstructed.
If you suspect ureteral kinking or obstruction
Consider removing any suspensory sutures near the obstructed (noneffluxing) ureter. This maneuver usually results in vigorous efflux from the affected orifice.10 In the case of apical suspension sutures, remove the most lateral suture first and perform cystoscopy after each (more medial) suture is removed.4,9
If suture removal fails to bring about ureteral efflux, evaluate the ureters further by using intraoperative retrograde ureterogram (pyelogram) under fluoroscopy or by placing ureteral stents under cystoscopic guidance. Either method will localize the obstruction or kink and allow for targeted exploration and release of the stricture.
Extended bladder drainage is usually not required after intraoperative release of a partially or completely obstructed ureter.
In my practice, I remove any permanent suture I suspect is kinking or partially kinking a ureter. If the suture causing the problem is an absorbable one (eg, as in the use of Vicryl suture at colpocleisis), I may choose to follow the patient or to place a stent, and I reassure the woman that the offending suture will dissolve over time, thus relieving the partial obstruction.
If blue dye enters the field from inside the pelvis
The problem may be partial or complete ureteral transection. In this case, bladder perforation must first be ruled out cystoscopically. Then perform retrograde ureterogram under fluoroscopy to look for the possible point of leakage.
If ureteral transection is confirmed, plan for thorough surgical exploration (usually via the abdominal route) to locate and repair the injury.
For many generalists, this may require an intraoperative consult from a surgical service comfortable with the repair and/or reimplantation of the ureters.
CASE 1 OUTCOME
The bladder laceration was repaired after completion of the vaginal hysterectomy in the manner described above. There were no further sequelae.
It pays to refamiliarize yourself with the particular “landscape” of the lower urinary tract, so that sutures or scalpels don’t inadvertently block or injure structures.
The smooth muscle of the bladder (detrusor) is lined with transitional mucosal epithelium and opens into the urethra at the bladder neck.
The ureters enter into the lateral aspects of the midposterior bladder and tunnel medially through the detrusor muscle before entering the bladder lumen at the level of the interureteral ridge. These entry points are known as the ureteral orifices.
The trigone is an area of the posterior bladder wall bounded by the bladder neck inferiorly and by the 2 ureteral orifices in the posterior midbladder.
Rectal injuries are usually easy to identify
As far as vaginal surgery is concerned, the lower GI tract consists of the rectum and external and internal anal sphincters. The distal rectum and posterior vaginal wall are usually closely applied to each other, separated by the rectovaginal septum (also called Denonvilliers fascia).
Risk factors
In women who have undergone posterior colporrhaphy or repair of a 4th degree tear, the posterior vaginal wall can be densely adherent to the rectum, putting the rectum at risk for injury during posterior vaginal wall dissection.
Most injuries to the rectum occur during dissection of the posterior vaginal wall. Fortunately, these injuries are readily recognized and easily repaired. If a rectal injury is suspected during or after dissection, a thorough intraoperative digital exam will help confirm or rule it out.
Repair of a rectal injury
Once an injury is identified, reapproximate the rectal mucosal edges with an imbricating closure using 3-0 Monocryl or other absorbable monofilament suture. A second imbricating layer should bring the rectal muscularis together, and the rectovaginal septum can then be closed over this layer in side-to-side or transverse fashion. Finally, close the vaginal mucosa after appropriate posterior colporrhaphy trimming. Such repairs heal well over time, without any long-term effects for the patient.
Prescribe a stool softener for the first 3 postoperative months to reduce the patient’s need to strain.
No bowel prep needed because injuries are rare
In my practice, the vast majority of vaginal surgical cases are accomplished without the need for preoperative bowel preparation. In the occasional patient known to have dense small-bowel adhesions involving the uterus, adnexae, or vaginal cuff, bowel prep may be appropriate if substantial dissection of the bowel is anticipated as part of the procedure.
CASE 2 Small bowel laceration
A 45-year-old woman with 4 prior vaginal deliveries, a 4th-degree obstetric rectovaginal laceration, and a history of laparoscopically assisted vaginal hysterectomy presents with stage III pelvic organ prolapse, primarily involving the posterior vaginal wall. An examination reveals a defect in the upper aspect of the posterior wall (an apical defect).
Intraoperatively, during sharp dissection to lift the posterior vaginal wall off the rectovaginal septum, a loop of small bowel descends into the field, and a 1-cm laceration occurs, exposing the lumen of the bowel.
How do you proceed?
On very rare occasions, a patient with an enterocele may sustain a small bowel injury during vaginal surgery. Such injury can usually be avoided by packing the small bowel away from the area of dissection and closely observing the dissection field.
Transvaginal repair
If the small bowel is cut during dissection, inspect the adjacent small bowel thoroughly to ascertain the extent of the injury. Transvaginal repair is recommended if the laceration and adjacent mesentery can be completely visualized and accessed through the vagina.
Small lacerations require a simple closure
If the laceration is small (1–2 cm) and does not involve the mesentery, irrigate it thoroughly and close it using a running imbricating 2-0 braided suture (eg, Vicryl or silk), with the suture line perpendicular to the long axis of the small bowel to decrease the risk of stricture. Inspect the suture line to ensure that it completely seals the laceration. Suture bites should incorporate the serosa and muscularis without transgressing the mucosa. Use a noncutting needle to place these sutures.
If the mesentery is involved in the laceration, make sure there are no bleeding vessels, and ligate any bleeding ones.
Large lacerations may necessitate abdominal surgery
An abdominal or laparoscopic procedure may be necessary to repair larger lacerations to the small bowel. If the surgeon is uncomfortable with bowel repair, it may be appropriate to obtain an intraoperative consult from a surgical service.
Postoperative monitoring
Watch for signs of ileus, which should be managed with bowel rest and nasogastric suction, as indicated.
CASE 2 OUTCOME
The small laceration was repaired with 2-0 Vicryl suture in the manner described above. The patient’s diet was advanced when bowel sounds returned. There were no further sequelae.
Generalists can manage most injuries
Incidental intraoperative injuries to the lower urinary and gastrointestinal tracts are relatively rare complications of vaginal surgery—but we must make every effort to anticipate, prevent, and promptly recognize such injuries.
If they do occur, pursue a course to thoroughly evaluate, repair, test, and provide appropriate followup for the patient. If promptly identified and addressed, these injuries can be made to resolve with minimal long-term sequelae. Appropriately timed intraoperative cystoscopy is a useful method for prompt intraoperative identification of bladder and ureteric injuries. Injuries identified intraoperatively can usually be repaired using simple techniques available to the general gynecologist.
The author reports no financial relationships relevant to this article
1. Gilmour DT, Baskett TF. Disability and litigation from urinary tract injuries at benign gynecologic surgery in Canada. Obstet Gynecol. 2005;105:109-114.
2. Pettit PD, Petrou SP. The value of cystoscopy in major vaginal surgery. Obstet Gynecol. 1994;84:318-320.
3. Gilmour DT, Dwyer PL, Carey MP. Lower urinary tract injury during gynecologic surgery and its detection by intraoperative cystoscopy. Obstet Gynecol. 1999;94:883-889.
4. Karram M, Goldwasser S, Kleeman S, et al. High uterosacral vaginal vault suspension with fascial reconstruction for vaginal repair of enterocele and vaginal vault prolapse. Am J Obstet Gynecol. 2001;185:1339-1342discussion 1342-1343.
5. Dowling RA, Corriere JN, Jr, Sandler CM. Iatrogenic ureteral injury. J Urol. 1986;135:912-915.
6. Mercer-Jones MA, Sprowson A, Varma JS. Outcome after transperineal mesh repair of rectocele: a case series. Dis Colon Rectum. 2004;47:864-868.
7. McLennan MT, Melick CF. Bladder perforation during tension-free vaginal tape procedures: analysis of learning curve and risk factors. Obstet Gynecol. 2005;106:1000-1004.
8. Leboeuf L, Tellez CA, Ead D, Gousse AE. Complication of bowel perforation during insertion of tension-free vaginal tape. J Urol. 2003;170:1310-discussion 1310-1311.
9. Shull BL, Bachofen C, Coates KW, Kuehl TJ. A transvaginal approach to repair of apical and other associated sites of pelvic organ prolapse with uterosacral ligaments. Am J Obstet Gynecol. 2000;183:1365-1373discussion 1373-1374.
10. Harris RL, Cundiff GW, Theofrastous JP, et al. The value of intraoperative cystoscopy in urogynecologic and reconstructive pelvic surgery. Am J Obstet Gynecol. 1997;177:1367-1369discussion 1369-1371.
1. Gilmour DT, Baskett TF. Disability and litigation from urinary tract injuries at benign gynecologic surgery in Canada. Obstet Gynecol. 2005;105:109-114.
2. Pettit PD, Petrou SP. The value of cystoscopy in major vaginal surgery. Obstet Gynecol. 1994;84:318-320.
3. Gilmour DT, Dwyer PL, Carey MP. Lower urinary tract injury during gynecologic surgery and its detection by intraoperative cystoscopy. Obstet Gynecol. 1999;94:883-889.
4. Karram M, Goldwasser S, Kleeman S, et al. High uterosacral vaginal vault suspension with fascial reconstruction for vaginal repair of enterocele and vaginal vault prolapse. Am J Obstet Gynecol. 2001;185:1339-1342discussion 1342-1343.
5. Dowling RA, Corriere JN, Jr, Sandler CM. Iatrogenic ureteral injury. J Urol. 1986;135:912-915.
6. Mercer-Jones MA, Sprowson A, Varma JS. Outcome after transperineal mesh repair of rectocele: a case series. Dis Colon Rectum. 2004;47:864-868.
7. McLennan MT, Melick CF. Bladder perforation during tension-free vaginal tape procedures: analysis of learning curve and risk factors. Obstet Gynecol. 2005;106:1000-1004.
8. Leboeuf L, Tellez CA, Ead D, Gousse AE. Complication of bowel perforation during insertion of tension-free vaginal tape. J Urol. 2003;170:1310-discussion 1310-1311.
9. Shull BL, Bachofen C, Coates KW, Kuehl TJ. A transvaginal approach to repair of apical and other associated sites of pelvic organ prolapse with uterosacral ligaments. Am J Obstet Gynecol. 2000;183:1365-1373discussion 1373-1374.
10. Harris RL, Cundiff GW, Theofrastous JP, et al. The value of intraoperative cystoscopy in urogynecologic and reconstructive pelvic surgery. Am J Obstet Gynecol. 1997;177:1367-1369discussion 1369-1371.
Assessing Health Literacy in Veterans with Diabetes
Multiple Metatarsal Fractures, Severe Foot Pain, and Intact Pulses
Diagnosis and safe management of placenta previa
CASE Diagnosis precedes sentinel episode of bleeding
“G.A.” is a 39-year-old gravida 6, para 1041 who was diagnosed with complete placenta previa during a target ultrasound exam performed at 18 weeks for advanced maternal age. She had a sentinel episode of vaginal bleeding at 29 weeks and was hospitalized for close monitoring.
Management strategy
One course of steroid was given, vaginal bleeding subsided, and she was discharged for outpatient conservative management, including iron and folic acid supplementation.
The outcome
The patient progressed to 36 weeks’ gestation, when she underwent amniocentesis to assess fetal lung maturity. When the results were reassuring, a cesarean section was scheduled. Intraoperative blood loss was diminished using pelvic vessel embolization. Surgery was uncomplicated, and a healthy infant was delivered.
Placenta previa is a leading and potentially life-threatening cause of third-trimester bleeding.1 Although the overall incidence is about 0.4% in pregnancies exceeding 20 weeks’ gestation,2 that figure rises with the number of cesarean sections and may reach 10% among women who have undergone 4 or more cesarean deliveries.3 Since more women are requesting elective and repeat cesarean deliveries, we are increasingly likely to encounter this condition.
Fortunately, technological advances have improved maternal and neonatal outcomes after placenta previa:
Nevertheless, the condition necessitates cesarean delivery and can cause serious maternal and perinatal morbidity, including:
It can also occur in association with vasa previa, which, though rare, carries a very high perinatal mortality rate.5
Risk factors
An enlarged placenta or endometrial disruption or scarring in the upper uterine segment due to 1 or more of the factors listed below may increase the likelihood of abnormal placental implantation in the unscarred lower uterine segment:3,6,7
Previa often begins with painless vaginal bleeding
The condition often presents as painless, bright red, vaginal bleeding in the third trimester. It is usually distinguished from abruptio placenta by the absence of abdominal pain and uterine contractions.5 However, approximately 20% of women have uterine activity associated with the first episode of vaginal bleeding.13,14 Moreover, in some cases, painful contractions and labor may precipitate vaginal bleeding from placenta previa.5 Therefore, ultrasound examination is strongly recommended for all women with vaginal bleeding during pregnancy.
Ultrasound for other reasons uncovers many cases
With greater routine use of ultrasonography in obstetrics, a large percentage of women with placenta previa are diagnosed prior to the onset of the characteristic painless vaginal bleeding. In a 2003 study by Dola and colleagues,15 approximately 43% of placenta previa cases were diagnosed by ultrasonography performed for other obstetrical indications prior to the onset of vaginal bleeding.
Look for “warning hemorrhage”
The first episode of vaginal bleeding is rarely profuse or life-threatening to the mother or fetus. The bleeding usually subsides spontaneously, although it could recur and become more severe with subsequent episodes. Pregnancy typically continues after the initial bleeding episode.
The mean gestational age at the time of the first bleeding is 29 to 32 weeks.13,14 However, a third of cases have vaginal bleeding before the 30th week of gestation, a third between 30 and 36 weeks, and a third after 36 weeks’ gestation.13-15 Ten percent of women with the condition may be completely asymptomatic and progress to 38 weeks’ gestation without vaginal bleeding.13,14
Which form of ultrasound is most accurate?
With the advanced technology available today, ultrasound has become the standard means of diagnosing placenta previa.16,17
Transabdominal ultrasound has accuracy as high as 95% and a false-negative rate of 7% in the diagnosis of placenta previa.13,19 However, its accuracy may be adversely affected by maternal obesity, acoustic shadowing of the fetal head in a cephalic presentation, inability to locate the internal cervical os (which is critical for correct diagnosis), and difficulty imaging a posterior placenta and the lateral uterine walls. In addition, a full maternal bladder—usually helpful in transabdominal ultrasound imaging—may cause a false-positive diagnosis if the bladder is overly distended. In this situation, the cervix would appear artificially elongated and give a normally implanted placenta the appearance of encroachment into the internal cervical os.
Transvaginal ultrasound is superior for diagnosis of previa
Leerentveld et al20 reported false-positive and false-negative rates of 1% and 2%, respectively—a striking improvement over transabdominal ultrasound, which has rates of 2% to 6% and 7%, respectively.
Transvaginal sonography has several advantages over transabdominal imaging in localization of the placenta. The shorter distance from the vaginal probe transducer to the cervix and lower uterine segment allows the use of higher-frequency ultrasound waves, with improved resolution; therefore, the relationship between the placental edge and the internal os can be determined more accurately.
Some clinicians may worry that the probe used in transvaginal sonography will disrupt the placenta and provoke significant maternal hemorrhage, but this concern is unfounded. Multiple studies have attested to the safety of transvaginal sonography in localization of the placenta.5,20-22 The probe is introduced and positioned under direct ultrasound guidance at all times, and inadvertent insertion of the endovaginal probe into the internal cervical os is virtually impossible due to the anatomical relationship of the vagina and cervix.21
Transperineal ultrasound is another option. Several investigators have found it to be superior to transabdominal and similarly advantageous to transvaginal sonography in the diagnosis and exclusion of placenta previa.18
Start with transabdominal imaging
In current practice, transabdominal ultrasound is usually performed first to localize the placenta. If there is reason to suspect placenta previa, transvaginal or transperineal sonography is then used to confirm the location of the placenta.
Contractions may hinder imaging
Accurate diagnosis or exclusion of placenta previa may be difficult if uterine contractions are present during ultrasound evaluation. Myometrial contractions shorten the distance between the internal cervical os and the placental edge, altering measurement of this distance. In addition, the ultrasound appearance of a contraction may simulate placental tissue, making it difficult to exclude placenta previa.
The trouble with tradition
The 4 types of placenta previa in the traditional classification system—complete, partial, marginal, and low-lying—predate the era of ultrasound diagnosis and are based on digital palpation of the placenta through a partly dilated cervical os during labor.
A new system of 3 types
Along with other authors,5,15-18 we propose a new system with 3 categories—complete, incomplete, and low-lying—because ultrasound may not distinguish a placenta partially covering the internal os (a discrete point) from one that is merely encroaching on it.
Complete previa
The placenta completely covers the internal cervical os
Incomplete previa
The placental edge is within 2 cm of the internal cervical os, but does not cover the os
Low-lying previa
The distance from the internal cervical os to the placental edge is between 2 and 3.5 cm
Look for placenta accreta
When placenta previa is diagnosed by ultrasound examination, further diagnostic measures are needed to determine whether placenta accreta is present.5,23 In placenta accreta, neither the normal plane of separation between the placental villi and uterine wall, nor the intervening fibrinoid layer of Nitabuch, is present.5,23
Degrees of abnormal placental implantation
Risk of accreta can reach 67%
There are varying reports on the incidence of placenta accreta, but women with placenta previa and previous cesarean deliveries appear to have the highest incidence.3,23,24 In women with placenta previa and 1 previous cesarean section, the risk of placenta accreta has been estimated at 24%, but it increases to 67% for women with placenta previa and 4 previous cesarean sections.3
Sonographic appearance of placenta accreta
Certain characteristics are suggestive of placenta accreta25,26:
Unfortunately, diagnosis of placenta accreta is difficult prior to delivery, although transvaginal sonography and adjunctive color flow/power Doppler imaging with 2- and 3-dimensional techniques offer improved resolution and have yielded promising results in prenatal diagnosis.27-30
Magnetic resonance imaging (MRI) may also prove useful in detecting placental tissue invasion and evaluating the degree of invasion, especially in a posterior or lateral placenta previa or when there is invasion into the bladder.31-33
Gestational age, symptoms determine management
The management of women with placenta previa in the third trimester depends on the extent of maternal hemorrhage and the fetal gestational age. Clinical categories include:
Some asymptomatic cases resolve
Outpatient management is possible for women who have never bled after diagnosis in the second trimester. These women should abstain from intercourse, avoid digital examination after 20 weeks’ gestation, and immediately present to the hospital if there is any evidence of vaginal bleeding.34
Monthly ultrasound evaluations are necessary to determine whether placenta previa has resolved,34-37 since 90% of cases detected in the second trimester resolve by the third trimester.34 However, if placenta previa persists beyond 24 weeks’ gestation, there is a 50% risk that delivery will be complicated by it.35 If placenta previa persists after 32 weeks, that risk approaches 75%.35
2-fold risk of congenital malformations
Most investigators report a 2-fold increased risk of fetal congenital malformations in cases of placenta previa.5 These malformations include anomalies of the central nervous system, cardiovascular system, respiratory tract, and gastrointestinal tract. Therefore, a target ultrasound examination for fetal anatomy is recommended at the initial ultrasound diagnosis of placenta previa.
Risk of fetal growth restriction warrants heightened surveillance
Some controversy surrounds the incidence of fetal growth restriction in pregnancies complicated by placenta previa. Varma38 reported that fetal growth restriction occurs in 16% of women with placenta previa and is correlated with the number of antepartum bleeding episodes. Other investigators have reported normal fetal growth in women with placenta previa.39 Given this uncertainty, serial follow-up ultrasound evaluations are usually advised for fetal growth assessment.
When patient remains asymptomatic, perform amniocentesis at 36 weeks
Some women progress to the late third trimester without any vaginal bleeding. In these women, amniocentesis is recommended at approximately 36 weeks’ gestation to assess fetal lung maturity.34,40 Elective cesarean delivery can then be planned if pulmonary maturity is documented.
The benefits of elective delivery include a stable patient and an optimally prepared surgical team, as well as the avoidance of emergent surgery, which increases the risk for maternal complications. Emergent surgery also places the fetus at greater risk for anemia, compared with elective procedures(27.7% vs 2.9%, respectively).13
Vaginal bleeding requires inpatient evaluation
Any woman with placenta previa who presents with vaginal bleeding should be admitted to the labor and delivery unit for immediate evaluation of maternal and fetal status, including an estimation of gestational age.
Initial acute care and assessment necessitate34:
If hemorrhage is life-threatening, deliver immediately
During initial evaluation, if the hemorrhage is judged to be massive and life-threatening, resuscitative measures and immediate delivery are necessary to avoid serious maternal morbidity. Recommended measures include constant monitoring of maternal status, aggressive IV fluid resuscitation, transfusion of blood and blood products, assessment of fetal status, and immediate delivery without regard to the maturity of the fetus.
A woman at term or near term (with documented fetal lung maturity) who presents with mild or moderate vaginal bleeding should be delivered via cesarean section.
Conservative management may be appropriate for mild preterm bleeding
If vaginal bleeding is not threatening to the life of the mother, and the fetus is preterm, a conservative approach with aggressive expectant management is appropriate, since most first episodes of vaginal bleeding are self-limited and rarely life-threatening to mother or fetus. Expectant management allows fetal maturation in utero without jeopardizing maternal health. If maternal and fetal health remain stable, the expectant approach allows a safe delay of delivery until the fetus matures.
Hospitalization is recommended. Candidates for expectant management should be hospitalized after the initial episode of vaginal bleeding. Once maternal and fetal conditions stabilize, the woman should be transferred to the antepartum ward for hospital bed rest with bathroom privileges. For expectant management:
Delivery is warranted for life-threatening hemorrhage, fetal lung maturity, and/or the usual maternal and fetal indications.
The question of tocolysis
Third-trimester tocolytic therapy in a woman with vaginal bleeding is controversial. In placenta previa, vaginal bleeding appears to arise from disruption of the placental implantation site as the lower uterine segment develops.41,42 It is unclear whether uterine contractions play a role, as only 20% of women with placenta previa have uterine activity at the time of vaginal bleeding.13,14,42 It is difficult to determine whether these women have true preterm labor, because digital examination of the cervix to document cervical dilatation is impossible.
Does uterine activity precipitate bleeding?
Some investigators believe uterine activity is a predisposing factor for the vaginal bleeding associated with placenta previa, and would consider tocolytic therapy in a stable patient at a premature gestational age. However, further evidence of its safety is needed.
In particular, beta-mimetics should be avoided in hemorrhaging women because their vasodilatory effects can precipitate maternal hypotension. Another side effect of beta-mimetics: maternal tachycardia,43 which may mask the hypovolemic state in women with significant hemorrhage.
Magnesium sulfate has less effect on the maternal cardiovascular system and could be a better choice in symptomatic placenta previa.41 Also consider indomethacin, which appears to have fewer adverse maternal effects.
Inpatient vs outpatient management
Because 2 to 3 weeks of maternal hospitalization can pass between the initial warning hemorrhage and delivery of the fetus, outpatient care has become an option. Several retrospective studies have demonstrated the cost-effectiveness and safety of outpatient management of symptomatic placenta previa.44,45 These studies emphasized careful patient section.
Wing and associates46 conducted a prospective, randomized, controlled trial that reinforces the need for judicious use of outpatient management. In their study, fewer than half the patients diagnosed with placenta previa prior to 37 weeks were candidates. The authors point out the small number of patients in their study, and the fact that vaginal bleeding recurred in approximately 60% of patients. Because of the difficulty of predicting which patients will have recurrent bleeding and when, outpatient management should be reserved for those judged to be compliant with home bed rest who can rapidly return to the hospital, if necessary.
Women with recurrent vaginal bleeding during outpatient management should be rehospitalized.
In the event of massive hemorrhage, immediate compression of the aorta below the level of the renal arteries will reduce the bleeding enough to allow time to evaluate the situation.56 At the same time, aggressive IV fluid resuscitation and blood transfusion should begin. Reevaluate coagulation status after every 5 to 10 U of blood.57
Focused repair may be effective. In some situations, the hemorrhage may be controlled by oversewing and repairing the focal placental site defects.40
Bracketing the bleeding area. Another measure is a circular suture technique in which interrupted sutures are placed on the serosal surface of the anterior and posterior aspects of the uterus and as deeply as possible into the endometrium in a circumferential manner, bracketing the bleeding area.58
The argon beam coagulator can be used to achieve hemostasis; it is more effective than traditional bipolar cautery at ensuring hemostasis in extensive areas.56,57
Stepwise devascularization was effective in 100% of 103 women with postpartum hemorrhage who did not respond to traditional management.59 It involves 5 procedures to be performed in sequence until hemostasis is achieved: unilateral uterine vessel ligation, bilateral uterine vessel ligation, low uterine vessel ligation, unilateral ovarian vessel ligation, and bilateral ovarian vessel ligation.
Hypogastric artery ligation is another option, but it is technically challenging and successful in less than 50% of cases.57 In fact, the time spent on this technique may actually lead to increased blood loss.
Components of safe delivery
A detailed plan is necessary when major hemorrhage is anticipated at the time of elective cesarean delivery for placenta previa, including consultation with experts in different disciplines such as radiology, anesthesiology, urology, pathology, blood bank, neonatology, and gynecologic oncology.
Also pay attention to the maternal red blood cell reserve. Iron and folic acid should be administered to prevent and treat anemia, and antepartum erythropoietin should be considered as a way of increasing the hemoglobin level in women with placenta previa. Autologous blood transfusion, including acute normovolemic hemodilution, is another option.
Pelvic vessel embolization
Elective embolization or occlusion of the hypogastric or uterine arteries has proved to be safe and effective for postpartum hemorrhage, with a success rate of more than 90% in women with normal coagulation.47
In addition, elective catheterization with a balloon-tipped catheter can be used prophylactically to reduce blood flow to the placenta. Prophylactic catheterization of the anterior division of the internal iliac arteries can be performed right before the scheduled cesarean section. An axillary approach is technically easier for fluoroscopically guided catheterization of the internal iliac.48 The actual fluoroscopy time is minutes, so the risk of fetal exposure to radiation and irreversible ovarian damage is minimal.
The fetus is monitored during the procedure, and the balloons are left in the deflated state until after delivery, reducing the risk of uteroplacental insufficiency. Balloon inflation after delivery occludes the hypogastric arteries and diminishes uterine arterial blood flow during surgery. In some cases, the temporary occlusive effect of the balloons may control intraoperative bleeding completely. If substantial bleeding persists, subsequent embolization of the uterine arteries is advised, using absorbable Gelfoam particles, which are temporary and do not damage pelvic organs. Menstruation is not impaired, and normal pregnancies have been reported after this procedure.49,50
In women who undergo cesarean delivery under regional anesthesia, placement of a dry epidural catheter for later dosing of anesthetic agents should be considered prior to balloon catheterization, since the patient’s mobility is restricted after placement of the balloon-tipped catheter.
This therapy is especially useful when there is a high index of suspicion for placenta accreta.
Recommendations at the time of delivery
Hysterectomy for placenta previa, placenta accreta
This procedure is technically challenging when there is a markedly enlarged uterus with engorged collateral vessels. One useful method, delayed ligation technique, was originally described by Dyer et al on the Tulane obstetrics service at Charity Hospital of New Orleans.53 This technique facilitates quick control of all uterine vasculature with rapid hemostasis. Later modification of this method involves successive clamping and severing of all vascular pedicles supplying the uterus, prior to their suture ligation, for quick control of bleeding.
Close follow-up continues even after surgery
Immediately after surgery, close monitoring of hemodynamic status is required, ideally in a critical care setting. Because women with placenta previa/placenta accreta have often received massive transfusions of blood and blood products along with large volumes of crystalloid fluids, pulmonary edema may develop. Conversely, hypovolemia can result from inadequate replacement of blood or persistent intra-abdominal bleeding. Thus, close attention to urinary output allows early detection of pulmonary edema, acute respiratory distress syndrome, hypovolemia, or persistent intra-abdominal bleeding. Patients who undergo peripartum hysterectomy should also be monitored closely for possible ureteral injury.
Thromboprophylaxis should continue until the patient is ambulatory.
Recommended laboratory tests
Get a complete blood count with platelets and fibrinogen immediately after surgery and at frequent intervals as needed. A chemistry panel with calcium, albumin, electrolytes, and creatinine also is helpful.
Serious morbidity in 3% to 5% of women after emergent hysterectomy
Conditions such as acute respiratory distress syndrome from massive blood transfusion and pulmonary capillary leakage, acute tubular necrosis from renal failure, and pulmonary embolism may complicate 3% to 5% of cases.54
Reoperation for persistent intra-abdominal bleeding may be necessary, and 9% of women will have urologic injury. Unfortunately, the maternal mortality rate associated with this procedure is 0.8%, so meticulous postoperative care is mandated.55
The authors report no financial relationships with any company whose products are mentioned in this article.
1. Ananth CV, Savitz DA, Luther ER. Maternal cigarette smoking as a risk factor for placental abruption, placenta previa, and uterine bleeding in pregnancy. Am J Epidemiol. 1996;144:881-889.
2. Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med. 2003;13:175.-
3. Clark SL, Koonings PP, et al. Placenta previa/accreta and prior cesarean section. Obstet Gynecol. 1985;66:89-92.
4. Neri A, Manor Y, Matityahu A, Blieden L. Placenta previa and congenital cardiac anomalies. Fetal Ther. 1989;4:138-140.
5. Clark SL. Placenta previa and abruptio placenta. In: Creasy RK, Resnik R. Maternal-Fetal Medicine, Principles and Practice. 4th ed. Philadelphia: W.B. Saunders; 1999:616–631.
6. Miller DA, Chollet J, Goodwin TM. Clinical risks factors for placenta previa-placenta accreta. Am J Obstet Gynecol. 1997;177:210-214.
7. Ananth CV, Demissie K, Smulian JC, Vintzileos AM. Placenta previa in singleton and twin births in the United States, 1989 through 1998: a comparison of risk factor profiles and associated conditions. Am J Obstet Gynecol. 2003;188:275-281.
8. Gilbert WM, Nesbitt TS, Danielsen B. Childbearing beyond age 40: pregnancy outcome in 24,032 cases. Obstet Gynecol. 1999;93:9-14.
9. Lavery JP. Placenta previa. Clin Obstet Gynecol. 1990;33:414-421.
10. Taylor VM, Kramer MD, Vaughan TL, Peacock S. Placenta previa in relation to induced and spontaneous abortion: a population- based study. Obstet Gynecol. 1993;82:88-91.
11. Williams MA, Mittendorf R, Lieberman E, Monson RR, Schoenbaum SC, Genest DR. Cigarette smoking during pregnancy in relation to placenta previa. Am J Obstet Gynecol. 1991;165:28-32.
12. Handler AS, Mason ED, Rosenberg DL, Davis FG. The relationship between exposure during pregnancy to cigarette smoking and cocaine use and placenta previa. Am J Obstet Gynecol. 1994;170:884-889.
13. Cotton DB, Read JA, Paul RH, Quilligan EJ. The conservative aggressive management of placenta previa. Am J Obstet Gynecol. 1980;137:687-695.
14. Silver R, Depp R, Sabbagha RE, Dooley SL. Placenta previa: aggressive expectant management. Am J Obstet Gynecol. 1984;150:15-22.
15. Dola CP, Garite TJ, Dowling DD, Friend D, Ahdoot D, Asrat T. Placenta previa: does its type affect pregnancy outcome? Am J Perinatol. 2003;20:353-360.
16. Oppenheimer LW, Farine D, Ritchie JWK, Lewinsky RM, Telford J, Fairbanks LA. What is low-lying placenta? Am J Obstet Gynecol. 1991;165:1036-1038.
17. Bhide A, Thilaganathan B. Recent advances in the management of placenta previa. Curr Opin Obstet Gynecol. 2004;16:447-451.
18. Dawson WB, Dumas MD, Romano WM, Gagnon R, Gratton RJ, Mowbray RD. Translabial ultrasonography and placenta previa: does measurement of the os-placenta distance predict outcome? J Ultrasound Med. 1996;15:44-46.
19. Egley CC. Abruptio placentae and placenta previa. In: Winn HN, Hobbins JC. Clinical Maternal-Fetal Medicine.1st ed. Pearl River, NY: Parthenon Publishing; 2000:47–53.
20. Leerentveld RA, Gilberts E, Arnold M, Wladimiroff JW. Accuracy and safety of transvaginal sonographic placental localization. Obstet Gynecol. 1990;76:759-762.
21. Timor-Tritsch I, Yunis R. Confirming the safety of transvaginal sonography in patients suspected of placenta previa. Obstet Gynecol. 1993;81:742-744.
22. Tan NH, Abu M, Woo JLS, Tahir H. The role of transvaginal sonography in the diagnosis of placenta previa. Aust NZ J Obstet Gynaecol. 1995;35:42-45.
23. Miller DA, Cholleet JA, Goodwin TM. Clinical risk factors for placenta previa-placenta accreta. Am J Obstet Gynecol. 1997;177:210-214.
24. Chattopadhyay SK, Kharif H, Sherbeeni MM. Placenta previa and accreta after previous cesarean section. Eur J Obstet Gynecol Reprod Biol. 1993;52:151.-
25. Comstock CH, Love JJ, Jr, Bronsteen RA, et al. Sonographic detection of placenta accreta in the second and third trimesters of pregnancy. Am J Obstet Gynecol. 2004;190:1135-1140.
26. Comstock CH, Lee W, Vettraino IM, Bronsteen RA. The early sonographic appearance of placenta accreta. J Ultrasound Med. 2003;22:19-23.
27. Chou MM, Ho ES. Prenatal diagnosis of placenta previa accreta with power amplitude ultrasonic agiography. Am J Obstet Gynecol. 1997;177:1523-1525.
28. Levine D, Hulka CA, Ludmir J, Li W, Edelman RR. Placenta accreta: evaluation with color Doppler US, power Doppler US, and MR imaging. Radiology. 1997;205:773-776.
29. Taipale P, Orden MR, Berg M, Manninen H, Alafuzoff I. Prenatal diagnosis of placenta accreta and percreta with ultrasonography, color Doppler, and magnetic resonance imaging. Obstet Gynecol. 2004;104:537-540.
30. Chou MM, Tseng JJ, Ho ES, Hwang JI. Three-dimensional color power Doppler imaging in the assessment of uteroplacental neovascularization in placenta previa increta/percreta. Am J Obstet Gynecol. 2001;185:1257-1260.
31. Maldjian C, Adam R, Pelosi M, II, Pelosi M III, Rudelli RD, Maldjian J. MRI appearance of placenta percreta and placenta accreta. Magnetic Resonance Imaging. 1999;17:965-971.
32. Thorp JM, Councell RB, Sandridge DA, Wiest HH. Antepartum diagnosis of placenta previa percreta by magnetic resonance imaging. Obstet Gynecol. 1992;80:506-508.
33. Kay HH, Spritzer CE. Preliminary experience with magnetic resonance imaging in patients with third-trimester bleeding. Obstet Gynecol. 1991;78:424-429.
34. Russo-Stieglitz K, Lockwood CJ. Placenta previa and vasa previa. Up To Date. 2005. Available at: www.uptodate.com.
35. Dashe JS, McIntire DD, Ramus RM, Santos-Ramos R, Twickler DM. Persistence of placenta previa according to gestational age at ultrasound detection. Obstet Gynecol. 2002;99:692-697.
36. Taipale P, Hiilesmaa V, Ylostalo P. Transvaginal ultrasonography at 18-23 weeks in predicting placenta previa at delivery. Ultrasound Obstet Gynecol. 1998;12:422.-
37. Rosati P, Guariglia L. Clinical significance of placenta previa detected at early routine transvaginal scan. J Ultrasound Med. 2000;19:581-585.
38. Varma TR. Fetal growth and placental function in patients with placenta previa. J Obstet Gynaecol Br Commonw. 1973;80:311-315.
39. Crane JM, Van Den Hof MC, et al. Neonatal outcomes with placenta previa. Obstet Gynecol. 1999;93:541-544.
40. Benedetti TJ. Obstetric hemorrhage. In: Gabbe SG, Niebyl, JR, Simpson JL. Obstetrics: Normal and Problem Pregnancies. 4th ed. Philadelphia: Churchill Livingstone; 2002:503–538.
41. Besinger RE, Moniak CW, Paskiewicz LS, et al. The effects of tocolytic use in the management of symptomatic placenta previa. Am J Obstet Gynecol. 1995;172:1770-1778.
42. Magann EF, Johnson CA, Gookin KS, Roberts WE, Martin RW, Morrison JC. Placenta praevia: does uterine activity cause bleeding? Aust NZ J Obstet Gynaecol. 1993;33:22-24
43. Benedetti TJ. Maternal complication of parenteral B-sympathomimetic therapy for premature labor. Am J Obstet Gynecol. 1983;145:1-6.
44. Mouer JR. Placenta previa: Antepartum conservative management, inpatient versus outpatient. Am J Obstet Gynecol. 1994;170:1683-1686.
45. Droste S, Keil K. Expectant management of placenta previa: cost-benefit analysis of outpatient treatment. Am J Obstet Gynecol. 1994;170:1254-1257.
46. Wing D, Paul RH, Millar LK. Management of the symptomatic placenta previa: a randomized, controlled trial of inpatient versus outpatient expectant management. Am J Obstet Gynecol. 1996;175:806-811.
47. 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. Am J Obstet Gynecol. 1999;180:1454-1460.
48. Dubois J, Garel L, Grignon A, Lemay M, Leduc L. Placenta percreta: balloon occlusion and embolization of the internal iliac arteries to reduce intraoperative blood losses. Am J Obstet Gynecol. 1997;176:723-726.
49. Suresh V, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization: an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol. 1997;176:938-948.
50. Salomon LJ, deTayrac R, Castaigne-Meary V, et al. Fertility and pregnancy outcome following pelvic arterial embolization for severe postpartum haemorrhage. A cohort study. Hum Reprod. 2003;18:849-852.
51. Frederiksen MC, Glassenberg R, Stika CS. Placenta previa: a 22-year analysis. Am J Obstet Gynecol. 1999;180:1432-1437.
52. Lockwood CJ, Artal R. Placenta accreta. Obstet Gynecol. 2002;99:1133-1134.
53. Dyer I, Nix GF, Weed JC. Total hysterectomy at cesarean section and the immediate puerperal period. Am J Obstet Gynecol. 1953;65:517-527.
54. Catanzarite VA, Stanco L, Schrimmer D, Conroy C. Managing placenta previa/accreta. Contemporary OB/GYN. 1996;4(5):66-95.
55. Stanco L, Schrimmer D, Paul D, Mishell D. Emergency peripartum hysterectomy and associated risk factors. Am J Obstet Gynecol. 1993;168:879-883.
56. Hudon L, Belfort MA, Broome DR. Diagnosis and management of placenta percreta: a review. Obstet Gynecol Surv. 1998;53:509-517.
57. Shevell T, Malone FD. Management of obstetric hemorrhage. Sem Perinatol. 2003;27:86-104.
58. Cho J, Kim S, Cha K, et al. Interrupted circular suture: bleeding control during cesarean delivery in placenta previa accreta. Obstet Gynecol. 1991;78:876-879.
59. AbdRabbo SA. Stepwise uterine devascularization: a novel technique for management of uncontrollable postpartum hemorrhage with preservation of the uterus. Am J Obstet Gynecol. 1994;171:694-700.
CASE Diagnosis precedes sentinel episode of bleeding
“G.A.” is a 39-year-old gravida 6, para 1041 who was diagnosed with complete placenta previa during a target ultrasound exam performed at 18 weeks for advanced maternal age. She had a sentinel episode of vaginal bleeding at 29 weeks and was hospitalized for close monitoring.
Management strategy
One course of steroid was given, vaginal bleeding subsided, and she was discharged for outpatient conservative management, including iron and folic acid supplementation.
The outcome
The patient progressed to 36 weeks’ gestation, when she underwent amniocentesis to assess fetal lung maturity. When the results were reassuring, a cesarean section was scheduled. Intraoperative blood loss was diminished using pelvic vessel embolization. Surgery was uncomplicated, and a healthy infant was delivered.
Placenta previa is a leading and potentially life-threatening cause of third-trimester bleeding.1 Although the overall incidence is about 0.4% in pregnancies exceeding 20 weeks’ gestation,2 that figure rises with the number of cesarean sections and may reach 10% among women who have undergone 4 or more cesarean deliveries.3 Since more women are requesting elective and repeat cesarean deliveries, we are increasingly likely to encounter this condition.
Fortunately, technological advances have improved maternal and neonatal outcomes after placenta previa:
Nevertheless, the condition necessitates cesarean delivery and can cause serious maternal and perinatal morbidity, including:
It can also occur in association with vasa previa, which, though rare, carries a very high perinatal mortality rate.5
Risk factors
An enlarged placenta or endometrial disruption or scarring in the upper uterine segment due to 1 or more of the factors listed below may increase the likelihood of abnormal placental implantation in the unscarred lower uterine segment:3,6,7
Previa often begins with painless vaginal bleeding
The condition often presents as painless, bright red, vaginal bleeding in the third trimester. It is usually distinguished from abruptio placenta by the absence of abdominal pain and uterine contractions.5 However, approximately 20% of women have uterine activity associated with the first episode of vaginal bleeding.13,14 Moreover, in some cases, painful contractions and labor may precipitate vaginal bleeding from placenta previa.5 Therefore, ultrasound examination is strongly recommended for all women with vaginal bleeding during pregnancy.
Ultrasound for other reasons uncovers many cases
With greater routine use of ultrasonography in obstetrics, a large percentage of women with placenta previa are diagnosed prior to the onset of the characteristic painless vaginal bleeding. In a 2003 study by Dola and colleagues,15 approximately 43% of placenta previa cases were diagnosed by ultrasonography performed for other obstetrical indications prior to the onset of vaginal bleeding.
Look for “warning hemorrhage”
The first episode of vaginal bleeding is rarely profuse or life-threatening to the mother or fetus. The bleeding usually subsides spontaneously, although it could recur and become more severe with subsequent episodes. Pregnancy typically continues after the initial bleeding episode.
The mean gestational age at the time of the first bleeding is 29 to 32 weeks.13,14 However, a third of cases have vaginal bleeding before the 30th week of gestation, a third between 30 and 36 weeks, and a third after 36 weeks’ gestation.13-15 Ten percent of women with the condition may be completely asymptomatic and progress to 38 weeks’ gestation without vaginal bleeding.13,14
Which form of ultrasound is most accurate?
With the advanced technology available today, ultrasound has become the standard means of diagnosing placenta previa.16,17
Transabdominal ultrasound has accuracy as high as 95% and a false-negative rate of 7% in the diagnosis of placenta previa.13,19 However, its accuracy may be adversely affected by maternal obesity, acoustic shadowing of the fetal head in a cephalic presentation, inability to locate the internal cervical os (which is critical for correct diagnosis), and difficulty imaging a posterior placenta and the lateral uterine walls. In addition, a full maternal bladder—usually helpful in transabdominal ultrasound imaging—may cause a false-positive diagnosis if the bladder is overly distended. In this situation, the cervix would appear artificially elongated and give a normally implanted placenta the appearance of encroachment into the internal cervical os.
Transvaginal ultrasound is superior for diagnosis of previa
Leerentveld et al20 reported false-positive and false-negative rates of 1% and 2%, respectively—a striking improvement over transabdominal ultrasound, which has rates of 2% to 6% and 7%, respectively.
Transvaginal sonography has several advantages over transabdominal imaging in localization of the placenta. The shorter distance from the vaginal probe transducer to the cervix and lower uterine segment allows the use of higher-frequency ultrasound waves, with improved resolution; therefore, the relationship between the placental edge and the internal os can be determined more accurately.
Some clinicians may worry that the probe used in transvaginal sonography will disrupt the placenta and provoke significant maternal hemorrhage, but this concern is unfounded. Multiple studies have attested to the safety of transvaginal sonography in localization of the placenta.5,20-22 The probe is introduced and positioned under direct ultrasound guidance at all times, and inadvertent insertion of the endovaginal probe into the internal cervical os is virtually impossible due to the anatomical relationship of the vagina and cervix.21
Transperineal ultrasound is another option. Several investigators have found it to be superior to transabdominal and similarly advantageous to transvaginal sonography in the diagnosis and exclusion of placenta previa.18
Start with transabdominal imaging
In current practice, transabdominal ultrasound is usually performed first to localize the placenta. If there is reason to suspect placenta previa, transvaginal or transperineal sonography is then used to confirm the location of the placenta.
Contractions may hinder imaging
Accurate diagnosis or exclusion of placenta previa may be difficult if uterine contractions are present during ultrasound evaluation. Myometrial contractions shorten the distance between the internal cervical os and the placental edge, altering measurement of this distance. In addition, the ultrasound appearance of a contraction may simulate placental tissue, making it difficult to exclude placenta previa.
The trouble with tradition
The 4 types of placenta previa in the traditional classification system—complete, partial, marginal, and low-lying—predate the era of ultrasound diagnosis and are based on digital palpation of the placenta through a partly dilated cervical os during labor.
A new system of 3 types
Along with other authors,5,15-18 we propose a new system with 3 categories—complete, incomplete, and low-lying—because ultrasound may not distinguish a placenta partially covering the internal os (a discrete point) from one that is merely encroaching on it.
Complete previa
The placenta completely covers the internal cervical os
Incomplete previa
The placental edge is within 2 cm of the internal cervical os, but does not cover the os
Low-lying previa
The distance from the internal cervical os to the placental edge is between 2 and 3.5 cm
Look for placenta accreta
When placenta previa is diagnosed by ultrasound examination, further diagnostic measures are needed to determine whether placenta accreta is present.5,23 In placenta accreta, neither the normal plane of separation between the placental villi and uterine wall, nor the intervening fibrinoid layer of Nitabuch, is present.5,23
Degrees of abnormal placental implantation
Risk of accreta can reach 67%
There are varying reports on the incidence of placenta accreta, but women with placenta previa and previous cesarean deliveries appear to have the highest incidence.3,23,24 In women with placenta previa and 1 previous cesarean section, the risk of placenta accreta has been estimated at 24%, but it increases to 67% for women with placenta previa and 4 previous cesarean sections.3
Sonographic appearance of placenta accreta
Certain characteristics are suggestive of placenta accreta25,26:
Unfortunately, diagnosis of placenta accreta is difficult prior to delivery, although transvaginal sonography and adjunctive color flow/power Doppler imaging with 2- and 3-dimensional techniques offer improved resolution and have yielded promising results in prenatal diagnosis.27-30
Magnetic resonance imaging (MRI) may also prove useful in detecting placental tissue invasion and evaluating the degree of invasion, especially in a posterior or lateral placenta previa or when there is invasion into the bladder.31-33
Gestational age, symptoms determine management
The management of women with placenta previa in the third trimester depends on the extent of maternal hemorrhage and the fetal gestational age. Clinical categories include:
Some asymptomatic cases resolve
Outpatient management is possible for women who have never bled after diagnosis in the second trimester. These women should abstain from intercourse, avoid digital examination after 20 weeks’ gestation, and immediately present to the hospital if there is any evidence of vaginal bleeding.34
Monthly ultrasound evaluations are necessary to determine whether placenta previa has resolved,34-37 since 90% of cases detected in the second trimester resolve by the third trimester.34 However, if placenta previa persists beyond 24 weeks’ gestation, there is a 50% risk that delivery will be complicated by it.35 If placenta previa persists after 32 weeks, that risk approaches 75%.35
2-fold risk of congenital malformations
Most investigators report a 2-fold increased risk of fetal congenital malformations in cases of placenta previa.5 These malformations include anomalies of the central nervous system, cardiovascular system, respiratory tract, and gastrointestinal tract. Therefore, a target ultrasound examination for fetal anatomy is recommended at the initial ultrasound diagnosis of placenta previa.
Risk of fetal growth restriction warrants heightened surveillance
Some controversy surrounds the incidence of fetal growth restriction in pregnancies complicated by placenta previa. Varma38 reported that fetal growth restriction occurs in 16% of women with placenta previa and is correlated with the number of antepartum bleeding episodes. Other investigators have reported normal fetal growth in women with placenta previa.39 Given this uncertainty, serial follow-up ultrasound evaluations are usually advised for fetal growth assessment.
When patient remains asymptomatic, perform amniocentesis at 36 weeks
Some women progress to the late third trimester without any vaginal bleeding. In these women, amniocentesis is recommended at approximately 36 weeks’ gestation to assess fetal lung maturity.34,40 Elective cesarean delivery can then be planned if pulmonary maturity is documented.
The benefits of elective delivery include a stable patient and an optimally prepared surgical team, as well as the avoidance of emergent surgery, which increases the risk for maternal complications. Emergent surgery also places the fetus at greater risk for anemia, compared with elective procedures(27.7% vs 2.9%, respectively).13
Vaginal bleeding requires inpatient evaluation
Any woman with placenta previa who presents with vaginal bleeding should be admitted to the labor and delivery unit for immediate evaluation of maternal and fetal status, including an estimation of gestational age.
Initial acute care and assessment necessitate34:
If hemorrhage is life-threatening, deliver immediately
During initial evaluation, if the hemorrhage is judged to be massive and life-threatening, resuscitative measures and immediate delivery are necessary to avoid serious maternal morbidity. Recommended measures include constant monitoring of maternal status, aggressive IV fluid resuscitation, transfusion of blood and blood products, assessment of fetal status, and immediate delivery without regard to the maturity of the fetus.
A woman at term or near term (with documented fetal lung maturity) who presents with mild or moderate vaginal bleeding should be delivered via cesarean section.
Conservative management may be appropriate for mild preterm bleeding
If vaginal bleeding is not threatening to the life of the mother, and the fetus is preterm, a conservative approach with aggressive expectant management is appropriate, since most first episodes of vaginal bleeding are self-limited and rarely life-threatening to mother or fetus. Expectant management allows fetal maturation in utero without jeopardizing maternal health. If maternal and fetal health remain stable, the expectant approach allows a safe delay of delivery until the fetus matures.
Hospitalization is recommended. Candidates for expectant management should be hospitalized after the initial episode of vaginal bleeding. Once maternal and fetal conditions stabilize, the woman should be transferred to the antepartum ward for hospital bed rest with bathroom privileges. For expectant management:
Delivery is warranted for life-threatening hemorrhage, fetal lung maturity, and/or the usual maternal and fetal indications.
The question of tocolysis
Third-trimester tocolytic therapy in a woman with vaginal bleeding is controversial. In placenta previa, vaginal bleeding appears to arise from disruption of the placental implantation site as the lower uterine segment develops.41,42 It is unclear whether uterine contractions play a role, as only 20% of women with placenta previa have uterine activity at the time of vaginal bleeding.13,14,42 It is difficult to determine whether these women have true preterm labor, because digital examination of the cervix to document cervical dilatation is impossible.
Does uterine activity precipitate bleeding?
Some investigators believe uterine activity is a predisposing factor for the vaginal bleeding associated with placenta previa, and would consider tocolytic therapy in a stable patient at a premature gestational age. However, further evidence of its safety is needed.
In particular, beta-mimetics should be avoided in hemorrhaging women because their vasodilatory effects can precipitate maternal hypotension. Another side effect of beta-mimetics: maternal tachycardia,43 which may mask the hypovolemic state in women with significant hemorrhage.
Magnesium sulfate has less effect on the maternal cardiovascular system and could be a better choice in symptomatic placenta previa.41 Also consider indomethacin, which appears to have fewer adverse maternal effects.
Inpatient vs outpatient management
Because 2 to 3 weeks of maternal hospitalization can pass between the initial warning hemorrhage and delivery of the fetus, outpatient care has become an option. Several retrospective studies have demonstrated the cost-effectiveness and safety of outpatient management of symptomatic placenta previa.44,45 These studies emphasized careful patient section.
Wing and associates46 conducted a prospective, randomized, controlled trial that reinforces the need for judicious use of outpatient management. In their study, fewer than half the patients diagnosed with placenta previa prior to 37 weeks were candidates. The authors point out the small number of patients in their study, and the fact that vaginal bleeding recurred in approximately 60% of patients. Because of the difficulty of predicting which patients will have recurrent bleeding and when, outpatient management should be reserved for those judged to be compliant with home bed rest who can rapidly return to the hospital, if necessary.
Women with recurrent vaginal bleeding during outpatient management should be rehospitalized.
In the event of massive hemorrhage, immediate compression of the aorta below the level of the renal arteries will reduce the bleeding enough to allow time to evaluate the situation.56 At the same time, aggressive IV fluid resuscitation and blood transfusion should begin. Reevaluate coagulation status after every 5 to 10 U of blood.57
Focused repair may be effective. In some situations, the hemorrhage may be controlled by oversewing and repairing the focal placental site defects.40
Bracketing the bleeding area. Another measure is a circular suture technique in which interrupted sutures are placed on the serosal surface of the anterior and posterior aspects of the uterus and as deeply as possible into the endometrium in a circumferential manner, bracketing the bleeding area.58
The argon beam coagulator can be used to achieve hemostasis; it is more effective than traditional bipolar cautery at ensuring hemostasis in extensive areas.56,57
Stepwise devascularization was effective in 100% of 103 women with postpartum hemorrhage who did not respond to traditional management.59 It involves 5 procedures to be performed in sequence until hemostasis is achieved: unilateral uterine vessel ligation, bilateral uterine vessel ligation, low uterine vessel ligation, unilateral ovarian vessel ligation, and bilateral ovarian vessel ligation.
Hypogastric artery ligation is another option, but it is technically challenging and successful in less than 50% of cases.57 In fact, the time spent on this technique may actually lead to increased blood loss.
Components of safe delivery
A detailed plan is necessary when major hemorrhage is anticipated at the time of elective cesarean delivery for placenta previa, including consultation with experts in different disciplines such as radiology, anesthesiology, urology, pathology, blood bank, neonatology, and gynecologic oncology.
Also pay attention to the maternal red blood cell reserve. Iron and folic acid should be administered to prevent and treat anemia, and antepartum erythropoietin should be considered as a way of increasing the hemoglobin level in women with placenta previa. Autologous blood transfusion, including acute normovolemic hemodilution, is another option.
Pelvic vessel embolization
Elective embolization or occlusion of the hypogastric or uterine arteries has proved to be safe and effective for postpartum hemorrhage, with a success rate of more than 90% in women with normal coagulation.47
In addition, elective catheterization with a balloon-tipped catheter can be used prophylactically to reduce blood flow to the placenta. Prophylactic catheterization of the anterior division of the internal iliac arteries can be performed right before the scheduled cesarean section. An axillary approach is technically easier for fluoroscopically guided catheterization of the internal iliac.48 The actual fluoroscopy time is minutes, so the risk of fetal exposure to radiation and irreversible ovarian damage is minimal.
The fetus is monitored during the procedure, and the balloons are left in the deflated state until after delivery, reducing the risk of uteroplacental insufficiency. Balloon inflation after delivery occludes the hypogastric arteries and diminishes uterine arterial blood flow during surgery. In some cases, the temporary occlusive effect of the balloons may control intraoperative bleeding completely. If substantial bleeding persists, subsequent embolization of the uterine arteries is advised, using absorbable Gelfoam particles, which are temporary and do not damage pelvic organs. Menstruation is not impaired, and normal pregnancies have been reported after this procedure.49,50
In women who undergo cesarean delivery under regional anesthesia, placement of a dry epidural catheter for later dosing of anesthetic agents should be considered prior to balloon catheterization, since the patient’s mobility is restricted after placement of the balloon-tipped catheter.
This therapy is especially useful when there is a high index of suspicion for placenta accreta.
Recommendations at the time of delivery
Hysterectomy for placenta previa, placenta accreta
This procedure is technically challenging when there is a markedly enlarged uterus with engorged collateral vessels. One useful method, delayed ligation technique, was originally described by Dyer et al on the Tulane obstetrics service at Charity Hospital of New Orleans.53 This technique facilitates quick control of all uterine vasculature with rapid hemostasis. Later modification of this method involves successive clamping and severing of all vascular pedicles supplying the uterus, prior to their suture ligation, for quick control of bleeding.
Close follow-up continues even after surgery
Immediately after surgery, close monitoring of hemodynamic status is required, ideally in a critical care setting. Because women with placenta previa/placenta accreta have often received massive transfusions of blood and blood products along with large volumes of crystalloid fluids, pulmonary edema may develop. Conversely, hypovolemia can result from inadequate replacement of blood or persistent intra-abdominal bleeding. Thus, close attention to urinary output allows early detection of pulmonary edema, acute respiratory distress syndrome, hypovolemia, or persistent intra-abdominal bleeding. Patients who undergo peripartum hysterectomy should also be monitored closely for possible ureteral injury.
Thromboprophylaxis should continue until the patient is ambulatory.
Recommended laboratory tests
Get a complete blood count with platelets and fibrinogen immediately after surgery and at frequent intervals as needed. A chemistry panel with calcium, albumin, electrolytes, and creatinine also is helpful.
Serious morbidity in 3% to 5% of women after emergent hysterectomy
Conditions such as acute respiratory distress syndrome from massive blood transfusion and pulmonary capillary leakage, acute tubular necrosis from renal failure, and pulmonary embolism may complicate 3% to 5% of cases.54
Reoperation for persistent intra-abdominal bleeding may be necessary, and 9% of women will have urologic injury. Unfortunately, the maternal mortality rate associated with this procedure is 0.8%, so meticulous postoperative care is mandated.55
The authors report no financial relationships with any company whose products are mentioned in this article.
CASE Diagnosis precedes sentinel episode of bleeding
“G.A.” is a 39-year-old gravida 6, para 1041 who was diagnosed with complete placenta previa during a target ultrasound exam performed at 18 weeks for advanced maternal age. She had a sentinel episode of vaginal bleeding at 29 weeks and was hospitalized for close monitoring.
Management strategy
One course of steroid was given, vaginal bleeding subsided, and she was discharged for outpatient conservative management, including iron and folic acid supplementation.
The outcome
The patient progressed to 36 weeks’ gestation, when she underwent amniocentesis to assess fetal lung maturity. When the results were reassuring, a cesarean section was scheduled. Intraoperative blood loss was diminished using pelvic vessel embolization. Surgery was uncomplicated, and a healthy infant was delivered.
Placenta previa is a leading and potentially life-threatening cause of third-trimester bleeding.1 Although the overall incidence is about 0.4% in pregnancies exceeding 20 weeks’ gestation,2 that figure rises with the number of cesarean sections and may reach 10% among women who have undergone 4 or more cesarean deliveries.3 Since more women are requesting elective and repeat cesarean deliveries, we are increasingly likely to encounter this condition.
Fortunately, technological advances have improved maternal and neonatal outcomes after placenta previa:
Nevertheless, the condition necessitates cesarean delivery and can cause serious maternal and perinatal morbidity, including:
It can also occur in association with vasa previa, which, though rare, carries a very high perinatal mortality rate.5
Risk factors
An enlarged placenta or endometrial disruption or scarring in the upper uterine segment due to 1 or more of the factors listed below may increase the likelihood of abnormal placental implantation in the unscarred lower uterine segment:3,6,7
Previa often begins with painless vaginal bleeding
The condition often presents as painless, bright red, vaginal bleeding in the third trimester. It is usually distinguished from abruptio placenta by the absence of abdominal pain and uterine contractions.5 However, approximately 20% of women have uterine activity associated with the first episode of vaginal bleeding.13,14 Moreover, in some cases, painful contractions and labor may precipitate vaginal bleeding from placenta previa.5 Therefore, ultrasound examination is strongly recommended for all women with vaginal bleeding during pregnancy.
Ultrasound for other reasons uncovers many cases
With greater routine use of ultrasonography in obstetrics, a large percentage of women with placenta previa are diagnosed prior to the onset of the characteristic painless vaginal bleeding. In a 2003 study by Dola and colleagues,15 approximately 43% of placenta previa cases were diagnosed by ultrasonography performed for other obstetrical indications prior to the onset of vaginal bleeding.
Look for “warning hemorrhage”
The first episode of vaginal bleeding is rarely profuse or life-threatening to the mother or fetus. The bleeding usually subsides spontaneously, although it could recur and become more severe with subsequent episodes. Pregnancy typically continues after the initial bleeding episode.
The mean gestational age at the time of the first bleeding is 29 to 32 weeks.13,14 However, a third of cases have vaginal bleeding before the 30th week of gestation, a third between 30 and 36 weeks, and a third after 36 weeks’ gestation.13-15 Ten percent of women with the condition may be completely asymptomatic and progress to 38 weeks’ gestation without vaginal bleeding.13,14
Which form of ultrasound is most accurate?
With the advanced technology available today, ultrasound has become the standard means of diagnosing placenta previa.16,17
Transabdominal ultrasound has accuracy as high as 95% and a false-negative rate of 7% in the diagnosis of placenta previa.13,19 However, its accuracy may be adversely affected by maternal obesity, acoustic shadowing of the fetal head in a cephalic presentation, inability to locate the internal cervical os (which is critical for correct diagnosis), and difficulty imaging a posterior placenta and the lateral uterine walls. In addition, a full maternal bladder—usually helpful in transabdominal ultrasound imaging—may cause a false-positive diagnosis if the bladder is overly distended. In this situation, the cervix would appear artificially elongated and give a normally implanted placenta the appearance of encroachment into the internal cervical os.
Transvaginal ultrasound is superior for diagnosis of previa
Leerentveld et al20 reported false-positive and false-negative rates of 1% and 2%, respectively—a striking improvement over transabdominal ultrasound, which has rates of 2% to 6% and 7%, respectively.
Transvaginal sonography has several advantages over transabdominal imaging in localization of the placenta. The shorter distance from the vaginal probe transducer to the cervix and lower uterine segment allows the use of higher-frequency ultrasound waves, with improved resolution; therefore, the relationship between the placental edge and the internal os can be determined more accurately.
Some clinicians may worry that the probe used in transvaginal sonography will disrupt the placenta and provoke significant maternal hemorrhage, but this concern is unfounded. Multiple studies have attested to the safety of transvaginal sonography in localization of the placenta.5,20-22 The probe is introduced and positioned under direct ultrasound guidance at all times, and inadvertent insertion of the endovaginal probe into the internal cervical os is virtually impossible due to the anatomical relationship of the vagina and cervix.21
Transperineal ultrasound is another option. Several investigators have found it to be superior to transabdominal and similarly advantageous to transvaginal sonography in the diagnosis and exclusion of placenta previa.18
Start with transabdominal imaging
In current practice, transabdominal ultrasound is usually performed first to localize the placenta. If there is reason to suspect placenta previa, transvaginal or transperineal sonography is then used to confirm the location of the placenta.
Contractions may hinder imaging
Accurate diagnosis or exclusion of placenta previa may be difficult if uterine contractions are present during ultrasound evaluation. Myometrial contractions shorten the distance between the internal cervical os and the placental edge, altering measurement of this distance. In addition, the ultrasound appearance of a contraction may simulate placental tissue, making it difficult to exclude placenta previa.
The trouble with tradition
The 4 types of placenta previa in the traditional classification system—complete, partial, marginal, and low-lying—predate the era of ultrasound diagnosis and are based on digital palpation of the placenta through a partly dilated cervical os during labor.
A new system of 3 types
Along with other authors,5,15-18 we propose a new system with 3 categories—complete, incomplete, and low-lying—because ultrasound may not distinguish a placenta partially covering the internal os (a discrete point) from one that is merely encroaching on it.
Complete previa
The placenta completely covers the internal cervical os
Incomplete previa
The placental edge is within 2 cm of the internal cervical os, but does not cover the os
Low-lying previa
The distance from the internal cervical os to the placental edge is between 2 and 3.5 cm
Look for placenta accreta
When placenta previa is diagnosed by ultrasound examination, further diagnostic measures are needed to determine whether placenta accreta is present.5,23 In placenta accreta, neither the normal plane of separation between the placental villi and uterine wall, nor the intervening fibrinoid layer of Nitabuch, is present.5,23
Degrees of abnormal placental implantation
Risk of accreta can reach 67%
There are varying reports on the incidence of placenta accreta, but women with placenta previa and previous cesarean deliveries appear to have the highest incidence.3,23,24 In women with placenta previa and 1 previous cesarean section, the risk of placenta accreta has been estimated at 24%, but it increases to 67% for women with placenta previa and 4 previous cesarean sections.3
Sonographic appearance of placenta accreta
Certain characteristics are suggestive of placenta accreta25,26:
Unfortunately, diagnosis of placenta accreta is difficult prior to delivery, although transvaginal sonography and adjunctive color flow/power Doppler imaging with 2- and 3-dimensional techniques offer improved resolution and have yielded promising results in prenatal diagnosis.27-30
Magnetic resonance imaging (MRI) may also prove useful in detecting placental tissue invasion and evaluating the degree of invasion, especially in a posterior or lateral placenta previa or when there is invasion into the bladder.31-33
Gestational age, symptoms determine management
The management of women with placenta previa in the third trimester depends on the extent of maternal hemorrhage and the fetal gestational age. Clinical categories include:
Some asymptomatic cases resolve
Outpatient management is possible for women who have never bled after diagnosis in the second trimester. These women should abstain from intercourse, avoid digital examination after 20 weeks’ gestation, and immediately present to the hospital if there is any evidence of vaginal bleeding.34
Monthly ultrasound evaluations are necessary to determine whether placenta previa has resolved,34-37 since 90% of cases detected in the second trimester resolve by the third trimester.34 However, if placenta previa persists beyond 24 weeks’ gestation, there is a 50% risk that delivery will be complicated by it.35 If placenta previa persists after 32 weeks, that risk approaches 75%.35
2-fold risk of congenital malformations
Most investigators report a 2-fold increased risk of fetal congenital malformations in cases of placenta previa.5 These malformations include anomalies of the central nervous system, cardiovascular system, respiratory tract, and gastrointestinal tract. Therefore, a target ultrasound examination for fetal anatomy is recommended at the initial ultrasound diagnosis of placenta previa.
Risk of fetal growth restriction warrants heightened surveillance
Some controversy surrounds the incidence of fetal growth restriction in pregnancies complicated by placenta previa. Varma38 reported that fetal growth restriction occurs in 16% of women with placenta previa and is correlated with the number of antepartum bleeding episodes. Other investigators have reported normal fetal growth in women with placenta previa.39 Given this uncertainty, serial follow-up ultrasound evaluations are usually advised for fetal growth assessment.
When patient remains asymptomatic, perform amniocentesis at 36 weeks
Some women progress to the late third trimester without any vaginal bleeding. In these women, amniocentesis is recommended at approximately 36 weeks’ gestation to assess fetal lung maturity.34,40 Elective cesarean delivery can then be planned if pulmonary maturity is documented.
The benefits of elective delivery include a stable patient and an optimally prepared surgical team, as well as the avoidance of emergent surgery, which increases the risk for maternal complications. Emergent surgery also places the fetus at greater risk for anemia, compared with elective procedures(27.7% vs 2.9%, respectively).13
Vaginal bleeding requires inpatient evaluation
Any woman with placenta previa who presents with vaginal bleeding should be admitted to the labor and delivery unit for immediate evaluation of maternal and fetal status, including an estimation of gestational age.
Initial acute care and assessment necessitate34:
If hemorrhage is life-threatening, deliver immediately
During initial evaluation, if the hemorrhage is judged to be massive and life-threatening, resuscitative measures and immediate delivery are necessary to avoid serious maternal morbidity. Recommended measures include constant monitoring of maternal status, aggressive IV fluid resuscitation, transfusion of blood and blood products, assessment of fetal status, and immediate delivery without regard to the maturity of the fetus.
A woman at term or near term (with documented fetal lung maturity) who presents with mild or moderate vaginal bleeding should be delivered via cesarean section.
Conservative management may be appropriate for mild preterm bleeding
If vaginal bleeding is not threatening to the life of the mother, and the fetus is preterm, a conservative approach with aggressive expectant management is appropriate, since most first episodes of vaginal bleeding are self-limited and rarely life-threatening to mother or fetus. Expectant management allows fetal maturation in utero without jeopardizing maternal health. If maternal and fetal health remain stable, the expectant approach allows a safe delay of delivery until the fetus matures.
Hospitalization is recommended. Candidates for expectant management should be hospitalized after the initial episode of vaginal bleeding. Once maternal and fetal conditions stabilize, the woman should be transferred to the antepartum ward for hospital bed rest with bathroom privileges. For expectant management:
Delivery is warranted for life-threatening hemorrhage, fetal lung maturity, and/or the usual maternal and fetal indications.
The question of tocolysis
Third-trimester tocolytic therapy in a woman with vaginal bleeding is controversial. In placenta previa, vaginal bleeding appears to arise from disruption of the placental implantation site as the lower uterine segment develops.41,42 It is unclear whether uterine contractions play a role, as only 20% of women with placenta previa have uterine activity at the time of vaginal bleeding.13,14,42 It is difficult to determine whether these women have true preterm labor, because digital examination of the cervix to document cervical dilatation is impossible.
Does uterine activity precipitate bleeding?
Some investigators believe uterine activity is a predisposing factor for the vaginal bleeding associated with placenta previa, and would consider tocolytic therapy in a stable patient at a premature gestational age. However, further evidence of its safety is needed.
In particular, beta-mimetics should be avoided in hemorrhaging women because their vasodilatory effects can precipitate maternal hypotension. Another side effect of beta-mimetics: maternal tachycardia,43 which may mask the hypovolemic state in women with significant hemorrhage.
Magnesium sulfate has less effect on the maternal cardiovascular system and could be a better choice in symptomatic placenta previa.41 Also consider indomethacin, which appears to have fewer adverse maternal effects.
Inpatient vs outpatient management
Because 2 to 3 weeks of maternal hospitalization can pass between the initial warning hemorrhage and delivery of the fetus, outpatient care has become an option. Several retrospective studies have demonstrated the cost-effectiveness and safety of outpatient management of symptomatic placenta previa.44,45 These studies emphasized careful patient section.
Wing and associates46 conducted a prospective, randomized, controlled trial that reinforces the need for judicious use of outpatient management. In their study, fewer than half the patients diagnosed with placenta previa prior to 37 weeks were candidates. The authors point out the small number of patients in their study, and the fact that vaginal bleeding recurred in approximately 60% of patients. Because of the difficulty of predicting which patients will have recurrent bleeding and when, outpatient management should be reserved for those judged to be compliant with home bed rest who can rapidly return to the hospital, if necessary.
Women with recurrent vaginal bleeding during outpatient management should be rehospitalized.
In the event of massive hemorrhage, immediate compression of the aorta below the level of the renal arteries will reduce the bleeding enough to allow time to evaluate the situation.56 At the same time, aggressive IV fluid resuscitation and blood transfusion should begin. Reevaluate coagulation status after every 5 to 10 U of blood.57
Focused repair may be effective. In some situations, the hemorrhage may be controlled by oversewing and repairing the focal placental site defects.40
Bracketing the bleeding area. Another measure is a circular suture technique in which interrupted sutures are placed on the serosal surface of the anterior and posterior aspects of the uterus and as deeply as possible into the endometrium in a circumferential manner, bracketing the bleeding area.58
The argon beam coagulator can be used to achieve hemostasis; it is more effective than traditional bipolar cautery at ensuring hemostasis in extensive areas.56,57
Stepwise devascularization was effective in 100% of 103 women with postpartum hemorrhage who did not respond to traditional management.59 It involves 5 procedures to be performed in sequence until hemostasis is achieved: unilateral uterine vessel ligation, bilateral uterine vessel ligation, low uterine vessel ligation, unilateral ovarian vessel ligation, and bilateral ovarian vessel ligation.
Hypogastric artery ligation is another option, but it is technically challenging and successful in less than 50% of cases.57 In fact, the time spent on this technique may actually lead to increased blood loss.
Components of safe delivery
A detailed plan is necessary when major hemorrhage is anticipated at the time of elective cesarean delivery for placenta previa, including consultation with experts in different disciplines such as radiology, anesthesiology, urology, pathology, blood bank, neonatology, and gynecologic oncology.
Also pay attention to the maternal red blood cell reserve. Iron and folic acid should be administered to prevent and treat anemia, and antepartum erythropoietin should be considered as a way of increasing the hemoglobin level in women with placenta previa. Autologous blood transfusion, including acute normovolemic hemodilution, is another option.
Pelvic vessel embolization
Elective embolization or occlusion of the hypogastric or uterine arteries has proved to be safe and effective for postpartum hemorrhage, with a success rate of more than 90% in women with normal coagulation.47
In addition, elective catheterization with a balloon-tipped catheter can be used prophylactically to reduce blood flow to the placenta. Prophylactic catheterization of the anterior division of the internal iliac arteries can be performed right before the scheduled cesarean section. An axillary approach is technically easier for fluoroscopically guided catheterization of the internal iliac.48 The actual fluoroscopy time is minutes, so the risk of fetal exposure to radiation and irreversible ovarian damage is minimal.
The fetus is monitored during the procedure, and the balloons are left in the deflated state until after delivery, reducing the risk of uteroplacental insufficiency. Balloon inflation after delivery occludes the hypogastric arteries and diminishes uterine arterial blood flow during surgery. In some cases, the temporary occlusive effect of the balloons may control intraoperative bleeding completely. If substantial bleeding persists, subsequent embolization of the uterine arteries is advised, using absorbable Gelfoam particles, which are temporary and do not damage pelvic organs. Menstruation is not impaired, and normal pregnancies have been reported after this procedure.49,50
In women who undergo cesarean delivery under regional anesthesia, placement of a dry epidural catheter for later dosing of anesthetic agents should be considered prior to balloon catheterization, since the patient’s mobility is restricted after placement of the balloon-tipped catheter.
This therapy is especially useful when there is a high index of suspicion for placenta accreta.
Recommendations at the time of delivery
Hysterectomy for placenta previa, placenta accreta
This procedure is technically challenging when there is a markedly enlarged uterus with engorged collateral vessels. One useful method, delayed ligation technique, was originally described by Dyer et al on the Tulane obstetrics service at Charity Hospital of New Orleans.53 This technique facilitates quick control of all uterine vasculature with rapid hemostasis. Later modification of this method involves successive clamping and severing of all vascular pedicles supplying the uterus, prior to their suture ligation, for quick control of bleeding.
Close follow-up continues even after surgery
Immediately after surgery, close monitoring of hemodynamic status is required, ideally in a critical care setting. Because women with placenta previa/placenta accreta have often received massive transfusions of blood and blood products along with large volumes of crystalloid fluids, pulmonary edema may develop. Conversely, hypovolemia can result from inadequate replacement of blood or persistent intra-abdominal bleeding. Thus, close attention to urinary output allows early detection of pulmonary edema, acute respiratory distress syndrome, hypovolemia, or persistent intra-abdominal bleeding. Patients who undergo peripartum hysterectomy should also be monitored closely for possible ureteral injury.
Thromboprophylaxis should continue until the patient is ambulatory.
Recommended laboratory tests
Get a complete blood count with platelets and fibrinogen immediately after surgery and at frequent intervals as needed. A chemistry panel with calcium, albumin, electrolytes, and creatinine also is helpful.
Serious morbidity in 3% to 5% of women after emergent hysterectomy
Conditions such as acute respiratory distress syndrome from massive blood transfusion and pulmonary capillary leakage, acute tubular necrosis from renal failure, and pulmonary embolism may complicate 3% to 5% of cases.54
Reoperation for persistent intra-abdominal bleeding may be necessary, and 9% of women will have urologic injury. Unfortunately, the maternal mortality rate associated with this procedure is 0.8%, so meticulous postoperative care is mandated.55
The authors report no financial relationships with any company whose products are mentioned in this article.
1. Ananth CV, Savitz DA, Luther ER. Maternal cigarette smoking as a risk factor for placental abruption, placenta previa, and uterine bleeding in pregnancy. Am J Epidemiol. 1996;144:881-889.
2. Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med. 2003;13:175.-
3. Clark SL, Koonings PP, et al. Placenta previa/accreta and prior cesarean section. Obstet Gynecol. 1985;66:89-92.
4. Neri A, Manor Y, Matityahu A, Blieden L. Placenta previa and congenital cardiac anomalies. Fetal Ther. 1989;4:138-140.
5. Clark SL. Placenta previa and abruptio placenta. In: Creasy RK, Resnik R. Maternal-Fetal Medicine, Principles and Practice. 4th ed. Philadelphia: W.B. Saunders; 1999:616–631.
6. Miller DA, Chollet J, Goodwin TM. Clinical risks factors for placenta previa-placenta accreta. Am J Obstet Gynecol. 1997;177:210-214.
7. Ananth CV, Demissie K, Smulian JC, Vintzileos AM. Placenta previa in singleton and twin births in the United States, 1989 through 1998: a comparison of risk factor profiles and associated conditions. Am J Obstet Gynecol. 2003;188:275-281.
8. Gilbert WM, Nesbitt TS, Danielsen B. Childbearing beyond age 40: pregnancy outcome in 24,032 cases. Obstet Gynecol. 1999;93:9-14.
9. Lavery JP. Placenta previa. Clin Obstet Gynecol. 1990;33:414-421.
10. Taylor VM, Kramer MD, Vaughan TL, Peacock S. Placenta previa in relation to induced and spontaneous abortion: a population- based study. Obstet Gynecol. 1993;82:88-91.
11. Williams MA, Mittendorf R, Lieberman E, Monson RR, Schoenbaum SC, Genest DR. Cigarette smoking during pregnancy in relation to placenta previa. Am J Obstet Gynecol. 1991;165:28-32.
12. Handler AS, Mason ED, Rosenberg DL, Davis FG. The relationship between exposure during pregnancy to cigarette smoking and cocaine use and placenta previa. Am J Obstet Gynecol. 1994;170:884-889.
13. Cotton DB, Read JA, Paul RH, Quilligan EJ. The conservative aggressive management of placenta previa. Am J Obstet Gynecol. 1980;137:687-695.
14. Silver R, Depp R, Sabbagha RE, Dooley SL. Placenta previa: aggressive expectant management. Am J Obstet Gynecol. 1984;150:15-22.
15. Dola CP, Garite TJ, Dowling DD, Friend D, Ahdoot D, Asrat T. Placenta previa: does its type affect pregnancy outcome? Am J Perinatol. 2003;20:353-360.
16. Oppenheimer LW, Farine D, Ritchie JWK, Lewinsky RM, Telford J, Fairbanks LA. What is low-lying placenta? Am J Obstet Gynecol. 1991;165:1036-1038.
17. Bhide A, Thilaganathan B. Recent advances in the management of placenta previa. Curr Opin Obstet Gynecol. 2004;16:447-451.
18. Dawson WB, Dumas MD, Romano WM, Gagnon R, Gratton RJ, Mowbray RD. Translabial ultrasonography and placenta previa: does measurement of the os-placenta distance predict outcome? J Ultrasound Med. 1996;15:44-46.
19. Egley CC. Abruptio placentae and placenta previa. In: Winn HN, Hobbins JC. Clinical Maternal-Fetal Medicine.1st ed. Pearl River, NY: Parthenon Publishing; 2000:47–53.
20. Leerentveld RA, Gilberts E, Arnold M, Wladimiroff JW. Accuracy and safety of transvaginal sonographic placental localization. Obstet Gynecol. 1990;76:759-762.
21. Timor-Tritsch I, Yunis R. Confirming the safety of transvaginal sonography in patients suspected of placenta previa. Obstet Gynecol. 1993;81:742-744.
22. Tan NH, Abu M, Woo JLS, Tahir H. The role of transvaginal sonography in the diagnosis of placenta previa. Aust NZ J Obstet Gynaecol. 1995;35:42-45.
23. Miller DA, Cholleet JA, Goodwin TM. Clinical risk factors for placenta previa-placenta accreta. Am J Obstet Gynecol. 1997;177:210-214.
24. Chattopadhyay SK, Kharif H, Sherbeeni MM. Placenta previa and accreta after previous cesarean section. Eur J Obstet Gynecol Reprod Biol. 1993;52:151.-
25. Comstock CH, Love JJ, Jr, Bronsteen RA, et al. Sonographic detection of placenta accreta in the second and third trimesters of pregnancy. Am J Obstet Gynecol. 2004;190:1135-1140.
26. Comstock CH, Lee W, Vettraino IM, Bronsteen RA. The early sonographic appearance of placenta accreta. J Ultrasound Med. 2003;22:19-23.
27. Chou MM, Ho ES. Prenatal diagnosis of placenta previa accreta with power amplitude ultrasonic agiography. Am J Obstet Gynecol. 1997;177:1523-1525.
28. Levine D, Hulka CA, Ludmir J, Li W, Edelman RR. Placenta accreta: evaluation with color Doppler US, power Doppler US, and MR imaging. Radiology. 1997;205:773-776.
29. Taipale P, Orden MR, Berg M, Manninen H, Alafuzoff I. Prenatal diagnosis of placenta accreta and percreta with ultrasonography, color Doppler, and magnetic resonance imaging. Obstet Gynecol. 2004;104:537-540.
30. Chou MM, Tseng JJ, Ho ES, Hwang JI. Three-dimensional color power Doppler imaging in the assessment of uteroplacental neovascularization in placenta previa increta/percreta. Am J Obstet Gynecol. 2001;185:1257-1260.
31. Maldjian C, Adam R, Pelosi M, II, Pelosi M III, Rudelli RD, Maldjian J. MRI appearance of placenta percreta and placenta accreta. Magnetic Resonance Imaging. 1999;17:965-971.
32. Thorp JM, Councell RB, Sandridge DA, Wiest HH. Antepartum diagnosis of placenta previa percreta by magnetic resonance imaging. Obstet Gynecol. 1992;80:506-508.
33. Kay HH, Spritzer CE. Preliminary experience with magnetic resonance imaging in patients with third-trimester bleeding. Obstet Gynecol. 1991;78:424-429.
34. Russo-Stieglitz K, Lockwood CJ. Placenta previa and vasa previa. Up To Date. 2005. Available at: www.uptodate.com.
35. Dashe JS, McIntire DD, Ramus RM, Santos-Ramos R, Twickler DM. Persistence of placenta previa according to gestational age at ultrasound detection. Obstet Gynecol. 2002;99:692-697.
36. Taipale P, Hiilesmaa V, Ylostalo P. Transvaginal ultrasonography at 18-23 weeks in predicting placenta previa at delivery. Ultrasound Obstet Gynecol. 1998;12:422.-
37. Rosati P, Guariglia L. Clinical significance of placenta previa detected at early routine transvaginal scan. J Ultrasound Med. 2000;19:581-585.
38. Varma TR. Fetal growth and placental function in patients with placenta previa. J Obstet Gynaecol Br Commonw. 1973;80:311-315.
39. Crane JM, Van Den Hof MC, et al. Neonatal outcomes with placenta previa. Obstet Gynecol. 1999;93:541-544.
40. Benedetti TJ. Obstetric hemorrhage. In: Gabbe SG, Niebyl, JR, Simpson JL. Obstetrics: Normal and Problem Pregnancies. 4th ed. Philadelphia: Churchill Livingstone; 2002:503–538.
41. Besinger RE, Moniak CW, Paskiewicz LS, et al. The effects of tocolytic use in the management of symptomatic placenta previa. Am J Obstet Gynecol. 1995;172:1770-1778.
42. Magann EF, Johnson CA, Gookin KS, Roberts WE, Martin RW, Morrison JC. Placenta praevia: does uterine activity cause bleeding? Aust NZ J Obstet Gynaecol. 1993;33:22-24
43. Benedetti TJ. Maternal complication of parenteral B-sympathomimetic therapy for premature labor. Am J Obstet Gynecol. 1983;145:1-6.
44. Mouer JR. Placenta previa: Antepartum conservative management, inpatient versus outpatient. Am J Obstet Gynecol. 1994;170:1683-1686.
45. Droste S, Keil K. Expectant management of placenta previa: cost-benefit analysis of outpatient treatment. Am J Obstet Gynecol. 1994;170:1254-1257.
46. Wing D, Paul RH, Millar LK. Management of the symptomatic placenta previa: a randomized, controlled trial of inpatient versus outpatient expectant management. Am J Obstet Gynecol. 1996;175:806-811.
47. 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. Am J Obstet Gynecol. 1999;180:1454-1460.
48. Dubois J, Garel L, Grignon A, Lemay M, Leduc L. Placenta percreta: balloon occlusion and embolization of the internal iliac arteries to reduce intraoperative blood losses. Am J Obstet Gynecol. 1997;176:723-726.
49. Suresh V, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization: an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol. 1997;176:938-948.
50. Salomon LJ, deTayrac R, Castaigne-Meary V, et al. Fertility and pregnancy outcome following pelvic arterial embolization for severe postpartum haemorrhage. A cohort study. Hum Reprod. 2003;18:849-852.
51. Frederiksen MC, Glassenberg R, Stika CS. Placenta previa: a 22-year analysis. Am J Obstet Gynecol. 1999;180:1432-1437.
52. Lockwood CJ, Artal R. Placenta accreta. Obstet Gynecol. 2002;99:1133-1134.
53. Dyer I, Nix GF, Weed JC. Total hysterectomy at cesarean section and the immediate puerperal period. Am J Obstet Gynecol. 1953;65:517-527.
54. Catanzarite VA, Stanco L, Schrimmer D, Conroy C. Managing placenta previa/accreta. Contemporary OB/GYN. 1996;4(5):66-95.
55. Stanco L, Schrimmer D, Paul D, Mishell D. Emergency peripartum hysterectomy and associated risk factors. Am J Obstet Gynecol. 1993;168:879-883.
56. Hudon L, Belfort MA, Broome DR. Diagnosis and management of placenta percreta: a review. Obstet Gynecol Surv. 1998;53:509-517.
57. Shevell T, Malone FD. Management of obstetric hemorrhage. Sem Perinatol. 2003;27:86-104.
58. Cho J, Kim S, Cha K, et al. Interrupted circular suture: bleeding control during cesarean delivery in placenta previa accreta. Obstet Gynecol. 1991;78:876-879.
59. AbdRabbo SA. Stepwise uterine devascularization: a novel technique for management of uncontrollable postpartum hemorrhage with preservation of the uterus. Am J Obstet Gynecol. 1994;171:694-700.
1. Ananth CV, Savitz DA, Luther ER. Maternal cigarette smoking as a risk factor for placental abruption, placenta previa, and uterine bleeding in pregnancy. Am J Epidemiol. 1996;144:881-889.
2. Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med. 2003;13:175.-
3. Clark SL, Koonings PP, et al. Placenta previa/accreta and prior cesarean section. Obstet Gynecol. 1985;66:89-92.
4. Neri A, Manor Y, Matityahu A, Blieden L. Placenta previa and congenital cardiac anomalies. Fetal Ther. 1989;4:138-140.
5. Clark SL. Placenta previa and abruptio placenta. In: Creasy RK, Resnik R. Maternal-Fetal Medicine, Principles and Practice. 4th ed. Philadelphia: W.B. Saunders; 1999:616–631.
6. Miller DA, Chollet J, Goodwin TM. Clinical risks factors for placenta previa-placenta accreta. Am J Obstet Gynecol. 1997;177:210-214.
7. Ananth CV, Demissie K, Smulian JC, Vintzileos AM. Placenta previa in singleton and twin births in the United States, 1989 through 1998: a comparison of risk factor profiles and associated conditions. Am J Obstet Gynecol. 2003;188:275-281.
8. Gilbert WM, Nesbitt TS, Danielsen B. Childbearing beyond age 40: pregnancy outcome in 24,032 cases. Obstet Gynecol. 1999;93:9-14.
9. Lavery JP. Placenta previa. Clin Obstet Gynecol. 1990;33:414-421.
10. Taylor VM, Kramer MD, Vaughan TL, Peacock S. Placenta previa in relation to induced and spontaneous abortion: a population- based study. Obstet Gynecol. 1993;82:88-91.
11. Williams MA, Mittendorf R, Lieberman E, Monson RR, Schoenbaum SC, Genest DR. Cigarette smoking during pregnancy in relation to placenta previa. Am J Obstet Gynecol. 1991;165:28-32.
12. Handler AS, Mason ED, Rosenberg DL, Davis FG. The relationship between exposure during pregnancy to cigarette smoking and cocaine use and placenta previa. Am J Obstet Gynecol. 1994;170:884-889.
13. Cotton DB, Read JA, Paul RH, Quilligan EJ. The conservative aggressive management of placenta previa. Am J Obstet Gynecol. 1980;137:687-695.
14. Silver R, Depp R, Sabbagha RE, Dooley SL. Placenta previa: aggressive expectant management. Am J Obstet Gynecol. 1984;150:15-22.
15. Dola CP, Garite TJ, Dowling DD, Friend D, Ahdoot D, Asrat T. Placenta previa: does its type affect pregnancy outcome? Am J Perinatol. 2003;20:353-360.
16. Oppenheimer LW, Farine D, Ritchie JWK, Lewinsky RM, Telford J, Fairbanks LA. What is low-lying placenta? Am J Obstet Gynecol. 1991;165:1036-1038.
17. Bhide A, Thilaganathan B. Recent advances in the management of placenta previa. Curr Opin Obstet Gynecol. 2004;16:447-451.
18. Dawson WB, Dumas MD, Romano WM, Gagnon R, Gratton RJ, Mowbray RD. Translabial ultrasonography and placenta previa: does measurement of the os-placenta distance predict outcome? J Ultrasound Med. 1996;15:44-46.
19. Egley CC. Abruptio placentae and placenta previa. In: Winn HN, Hobbins JC. Clinical Maternal-Fetal Medicine.1st ed. Pearl River, NY: Parthenon Publishing; 2000:47–53.
20. Leerentveld RA, Gilberts E, Arnold M, Wladimiroff JW. Accuracy and safety of transvaginal sonographic placental localization. Obstet Gynecol. 1990;76:759-762.
21. Timor-Tritsch I, Yunis R. Confirming the safety of transvaginal sonography in patients suspected of placenta previa. Obstet Gynecol. 1993;81:742-744.
22. Tan NH, Abu M, Woo JLS, Tahir H. The role of transvaginal sonography in the diagnosis of placenta previa. Aust NZ J Obstet Gynaecol. 1995;35:42-45.
23. Miller DA, Cholleet JA, Goodwin TM. Clinical risk factors for placenta previa-placenta accreta. Am J Obstet Gynecol. 1997;177:210-214.
24. Chattopadhyay SK, Kharif H, Sherbeeni MM. Placenta previa and accreta after previous cesarean section. Eur J Obstet Gynecol Reprod Biol. 1993;52:151.-
25. Comstock CH, Love JJ, Jr, Bronsteen RA, et al. Sonographic detection of placenta accreta in the second and third trimesters of pregnancy. Am J Obstet Gynecol. 2004;190:1135-1140.
26. Comstock CH, Lee W, Vettraino IM, Bronsteen RA. The early sonographic appearance of placenta accreta. J Ultrasound Med. 2003;22:19-23.
27. Chou MM, Ho ES. Prenatal diagnosis of placenta previa accreta with power amplitude ultrasonic agiography. Am J Obstet Gynecol. 1997;177:1523-1525.
28. Levine D, Hulka CA, Ludmir J, Li W, Edelman RR. Placenta accreta: evaluation with color Doppler US, power Doppler US, and MR imaging. Radiology. 1997;205:773-776.
29. Taipale P, Orden MR, Berg M, Manninen H, Alafuzoff I. Prenatal diagnosis of placenta accreta and percreta with ultrasonography, color Doppler, and magnetic resonance imaging. Obstet Gynecol. 2004;104:537-540.
30. Chou MM, Tseng JJ, Ho ES, Hwang JI. Three-dimensional color power Doppler imaging in the assessment of uteroplacental neovascularization in placenta previa increta/percreta. Am J Obstet Gynecol. 2001;185:1257-1260.
31. Maldjian C, Adam R, Pelosi M, II, Pelosi M III, Rudelli RD, Maldjian J. MRI appearance of placenta percreta and placenta accreta. Magnetic Resonance Imaging. 1999;17:965-971.
32. Thorp JM, Councell RB, Sandridge DA, Wiest HH. Antepartum diagnosis of placenta previa percreta by magnetic resonance imaging. Obstet Gynecol. 1992;80:506-508.
33. Kay HH, Spritzer CE. Preliminary experience with magnetic resonance imaging in patients with third-trimester bleeding. Obstet Gynecol. 1991;78:424-429.
34. Russo-Stieglitz K, Lockwood CJ. Placenta previa and vasa previa. Up To Date. 2005. Available at: www.uptodate.com.
35. Dashe JS, McIntire DD, Ramus RM, Santos-Ramos R, Twickler DM. Persistence of placenta previa according to gestational age at ultrasound detection. Obstet Gynecol. 2002;99:692-697.
36. Taipale P, Hiilesmaa V, Ylostalo P. Transvaginal ultrasonography at 18-23 weeks in predicting placenta previa at delivery. Ultrasound Obstet Gynecol. 1998;12:422.-
37. Rosati P, Guariglia L. Clinical significance of placenta previa detected at early routine transvaginal scan. J Ultrasound Med. 2000;19:581-585.
38. Varma TR. Fetal growth and placental function in patients with placenta previa. J Obstet Gynaecol Br Commonw. 1973;80:311-315.
39. Crane JM, Van Den Hof MC, et al. Neonatal outcomes with placenta previa. Obstet Gynecol. 1999;93:541-544.
40. Benedetti TJ. Obstetric hemorrhage. In: Gabbe SG, Niebyl, JR, Simpson JL. Obstetrics: Normal and Problem Pregnancies. 4th ed. Philadelphia: Churchill Livingstone; 2002:503–538.
41. Besinger RE, Moniak CW, Paskiewicz LS, et al. The effects of tocolytic use in the management of symptomatic placenta previa. Am J Obstet Gynecol. 1995;172:1770-1778.
42. Magann EF, Johnson CA, Gookin KS, Roberts WE, Martin RW, Morrison JC. Placenta praevia: does uterine activity cause bleeding? Aust NZ J Obstet Gynaecol. 1993;33:22-24
43. Benedetti TJ. Maternal complication of parenteral B-sympathomimetic therapy for premature labor. Am J Obstet Gynecol. 1983;145:1-6.
44. Mouer JR. Placenta previa: Antepartum conservative management, inpatient versus outpatient. Am J Obstet Gynecol. 1994;170:1683-1686.
45. Droste S, Keil K. Expectant management of placenta previa: cost-benefit analysis of outpatient treatment. Am J Obstet Gynecol. 1994;170:1254-1257.
46. Wing D, Paul RH, Millar LK. Management of the symptomatic placenta previa: a randomized, controlled trial of inpatient versus outpatient expectant management. Am J Obstet Gynecol. 1996;175:806-811.
47. 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. Am J Obstet Gynecol. 1999;180:1454-1460.
48. Dubois J, Garel L, Grignon A, Lemay M, Leduc L. Placenta percreta: balloon occlusion and embolization of the internal iliac arteries to reduce intraoperative blood losses. Am J Obstet Gynecol. 1997;176:723-726.
49. Suresh V, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization: an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol. 1997;176:938-948.
50. Salomon LJ, deTayrac R, Castaigne-Meary V, et al. Fertility and pregnancy outcome following pelvic arterial embolization for severe postpartum haemorrhage. A cohort study. Hum Reprod. 2003;18:849-852.
51. Frederiksen MC, Glassenberg R, Stika CS. Placenta previa: a 22-year analysis. Am J Obstet Gynecol. 1999;180:1432-1437.
52. Lockwood CJ, Artal R. Placenta accreta. Obstet Gynecol. 2002;99:1133-1134.
53. Dyer I, Nix GF, Weed JC. Total hysterectomy at cesarean section and the immediate puerperal period. Am J Obstet Gynecol. 1953;65:517-527.
54. Catanzarite VA, Stanco L, Schrimmer D, Conroy C. Managing placenta previa/accreta. Contemporary OB/GYN. 1996;4(5):66-95.
55. Stanco L, Schrimmer D, Paul D, Mishell D. Emergency peripartum hysterectomy and associated risk factors. Am J Obstet Gynecol. 1993;168:879-883.
56. Hudon L, Belfort MA, Broome DR. Diagnosis and management of placenta percreta: a review. Obstet Gynecol Surv. 1998;53:509-517.
57. Shevell T, Malone FD. Management of obstetric hemorrhage. Sem Perinatol. 2003;27:86-104.
58. Cho J, Kim S, Cha K, et al. Interrupted circular suture: bleeding control during cesarean delivery in placenta previa accreta. Obstet Gynecol. 1991;78:876-879.
59. AbdRabbo SA. Stepwise uterine devascularization: a novel technique for management of uncontrollable postpartum hemorrhage with preservation of the uterus. Am J Obstet Gynecol. 1994;171:694-700.
4 Cases that Test Your Skills: Workup for premenopausal breast complaints
What’s the most common cause of death in women 40 to 44 years of age?
Answer: Breast cancer.1
What population has the highest death toll from breast cancer?
Answer: Women age 40 and older. Approximately 95% of new breast cancer cases and 97% of breast cancer deaths occur in women 40 and older.2
Why are many women in their 40s under-screened?
Answer: Because clinicians sometimes under-appreciate their risk.
Of course, the majority of breast cancer cases and deaths involve postmenopausal women. But this doesn’t mean younger women don’t warrant heightened scrutiny. This article presents 4 cases that focus on breast disease in women 40 to 49 years of age and the optimal workup for patients with suspicious findings. It includes recommendations on:
Digital mammography may aid in evaluation of dense breast tissue
Although early breast cancer may be more difficult to identify on mammography in premenopausal women because of their denser breast tissue, there are good data on the benefits of screening mammography for women in the 40- to 49-year-old age group,3,4 as well as for women age 50 and older.5 In addition, digital mammography is often helpful in women with radiographically dense breasts.
Screening vs diagnostic mammography
Women who have no complaints and no abnormal physical findings on self- or clinical examination typically undergo screening mammography. In typical cases, 2 views of each breast are obtained, and the radiologist often postpones reading the images until the end of the day, when they are scrutinized in batches.
In contrast, diagnostic mammography is performed when a possible problem arises, and several additional “coned-down” views may be needed. The radiologist interprets the study while the patient is still in the radiology office.
It is essential that gynecologists indicate on the mammography referral form whether they are requesting a diagnostic or screening mammogram. If it is a diagnostic mammogram, the reason and precise location of any suspicious areas need to be clearly communicated to the radiologist. In either case, the patient should be reminded to provide any previous images the radiologist does not already have.
I obtain routine annual screening mammography for my average-risk patients from age 40 onward, since more than 50,000 American women under age 50 are diagnosed with breast cancer each year.
CASE 1 Abnormal mammogram
S.H. is a healthy 43-year-old who had vaginal deliveries at ages 25 and 28 and has always used barrier contraception. She has no family history of cancer or high-risk factors for breast cancer. Her breast and pelvic examinations at the time of her routine gynecologic visit are normal. She has undergone annual mammography since she was 40 years old, but recently moved from another state and did not bring her mammograms with her.
She is sent for a screening mammogram, and 2 radiographic views of each breast are obtained. Upon review, the images are classified as Breast Imaging Reporting and Data Systems (BI-RADS) category 0, indicating that mammographic assessment is incomplete. The radiologist wants additional images of an area in the upper outer quadrant of the right breast, and wants to compare this study with the patient’s old films if they are available. S.H. returns the next day for the additional imaging, and the radiologist identifies an 8-mm area of suspicious calcifications in the right breast, reclassifying the mammogram as BI-RADS category 4.
The radiologist recommends a stereotactic biopsy, but S.H. wants your advice on whether to comply or proceed immediately to open biopsy.
What do you tell her?
Barely invasive biopsy
Stereotactic needle biopsy offers precise positioning in 3 dimensions without the lag time and scarring associated with open biopsies.In the case above, stereotactic biopsy is a good option, since it can usually be scheduled rapidly, does not require an operating room or anesthesia, is less expensive than open biopsy, and involves less scarring.6 If a patient’s lesion is clearly benign on stereotactic biopsy, she may be spared an open biopsy. If it is malignant, she can immediately begin to make treatment decisions.
Breast imaging categories
BI-RADS categories have standardized the reporting of mammograms and include the following7:
S.H. schedules a stereotactic biopsy for the following day in the radiologist’s office. Tissue diagnosis reveals an invasive ductal carcinoma, and the patient elects to undergo lumpectomy and radiation therapy.
CASE 2 Self-palpated lesion
L.J., 45, has no personal or family history of cancer and no high-risk factors, and she has undergone annual mammograms since the age of 40. Her last mammogram, which was negative, was 3 months ago.
Today L.J. reports that she felt a 1-cm lesion in the upper outer quadrant of her left breast during monthly breast self-examination. Although she is somewhat reassured by the normal mammogram 3 months earlier, she had been instructed by her gynecologist to call if she ever had any abnormal findings on breast self-examination.
Her gynecologist performs a thorough history and physical examination of the breasts and lymph nodes, confirming the presence of the lesion but no other abnormalities.
What is the next step?
Self-examination and imaging don’t always agree
It is vital that a diagnosis be made whenever a mass is present in the breast—even if the mammogram is normal—since 10% to 15% of women with breast cancer have normal mammograms.1
In this case, the first step is to review the prior mammogram. If no abnormality is found on the mammogram, the patient should undergo further imaging to ascertain whether the lesion appears benign or suspicious for malignancy.
However, even if all radiologic studies are normal, definitive diagnosis is crucial when a mass is present.
MRI may be useful when other imaging is inconclusive
In 2004, the American College of Radiology (ACR) published guidelines for breast MRI,8 which advise against using the modality for breast cancer screening in the general population of asymptomatic women because of the likelihood of false positives. However, MRI is recommended by the ACR in a wide range of situations, including those in which other imaging such as mammography or ultrasound has been inconclusive.
I encourage self-examination
Because 75% of women diagnosed with breast cancer lack major high-risk factors, all women should be screened, and I believe self-examination should be encouraged. Although data from randomized controlled trials of breast self-examination do not confirm a reduction in overall breast cancer mortality with the practice, it may lead to earlier detection in some women.9
While L.J. is in the office, the gynecologist telephones the radiologist and asks her to review the mammogram. The radiologist does so, comparing the latest films with prior mammograms, and calls back to report the absence of abnormal findings.
The patient is then sent for ultrasound of the breast, which does not reveal a cyst but does show some suspicious changes. After a breast MRI is consistent with malignancy, the lesion is biopsied and diagnosed as invasive lobular carcinoma.
Mammography isn’t perfect. Neither is magnetic resonance imaging (MRI). But both can be revealing in the right patients. MRI studies suggest it is better at imaging soft tissues and can detect lesions not visible on mammogram in 27% to 37% of patients.12,13
The downside: cost. Because MRI is 10 to 15 times more costly than mammography, it is usually limited to patients with suspicious findings or high risk.
Higher predictive value, biopsy still needed
Bluemke DA, Catsonis CA, Chen MH, et al. Magnetic resonance imaging of the breast prior to biopsy. JAMA. 2004;292:2735–2742.
A prospective multicenter study by the International Breast MR Consortium involved 821 women referred for breast biopsy at 14 university hospitals in North America and Europe. All women had BI-RADS category 4 or 5 mammographic evaluation and breast MRI prior to the biopsy, with imaging interpreted at each site without knowledge of the biopsy results.
Findings: MRI correctly identified cancer in 356 of 404 cancer cases, for a sensitivity of 88.1% (95% confidence interval [CI] 84.6–91.1). It also correctly ruled out cancer in 281 of 417 cases with benign findings, for a specificity of 67.7% (95% CI 62.7–71.9). The positive predictive value of MRI for 356 of 492 patients was 72.4% (95% CI 68.2–76.3), compared with 52.8% for mammography in 367 of 695 patients (95% CI 49.0–56.6).
Conclusion: Despite the higher predictive value of MRI, tissue sampling is still needed when suspicious findings are detected.
Annual MRI and mammography for women at high risk
Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study. Lancet. 2005;365:1769–1778.
This prospective, multicenter study compared mammography with contrast-enhanced MRI in 649 women aged 35 to 49 who had a strong family history of breast cancer or a high probability of BRCA1, BRCA2, or TP53 mutation. The women had annual screening with both modalities for 2 to 7 years.
Findings: Thirtyfive cancers were diagnosed—19 by contrast-enhanced MRI only, 6 by mammography only, and 8 by both, with 2 “interval” cases. Sensitivity for contrast-enhanced MRI was significantly higher than for mammography (77% vs 40%; 95% CI 60–90 vs 24–58); when both modalities were used, it was 94% (95% CI 81–99). The contrast in sensitivity between the 2 modalities was particularly sharp in women with BRCA1 mutations: 92% for MRI vs 23% for mammography (P=.004). However, specificity was higher for mammography (93% vs 81%; 95% CI 92–95 vs 80–83); when both mammography and MRI were used, specificity was 77% (95% CI 75–79).
Leach et al noted a high proportion of grade 3 cancers in this study, but the tumors were small and most women were node-negative.
Conclusion: Annual screening with both contrast-enhanced MRI and mammography would detect most cancers in high-risk women.
MRI is more cost-effective in women with BRCA1/2 mutations
Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006;295:2374–2384.
Using a computer model to simulate the life histories of individual BRCA1 and BRCA2 mutation carriers, Plevritis et al compared mammography and breast MRI for cancer screening, using published data to estimate the accuracy of the 2 modalities. Breast cancer survival was based on the Surveillance, Epidemiology, and End Results (SEER) database, whereas utilization rates and intervention costs were based on published data and Medicare payments for 2005.
Findings: For each quality-adjusted life-year (QALY) gained, the cost of annual MRI in addition to annual mammography ranged from less than $45,000 to more than $700,000, depending on the patient’s age and specific BRCA mutation. Compared with mammography alone, the cost of MRI for each QALY gained in women aged 35 to 54 years was $55,420 for BRCA1 mutation carriers, $130,695 for BRCA2 mutation carriers, and $98,454 for BRCA2 mutation carriers with mammographically dense breasts.
Conclusion: Breast MRI screening is more cost-effective in women with BRCA1 mutations. The cost-effectiveness of adding it to mammography also varies greatly by age.
CASE 3 Bloody nipple discharge
M.W. is a 48-year-old nulliparous woman who has noticed blood in her bra in the area of the right nipple several times during the past month. Her last mammogram, which was normal, was 1 year ago. Her history lacks any relevant problems other than the nipple discharge itself. Her menstrual periods are regular; the last one was 2 weeks earlier. Many years ago, she underwent a tubal ligation. She does not take any medications.
How should she be evaluated?
Nipple discharge is a common phenomenon, more so among women with benign problems (approximately 10%–15%) than in women with malignancies (approximately 3%).10
When taking a history from a woman with nipple discharge, ask about the color of the discharge; whether it is bilateral; whether it is spontaneous; and its frequency and duration.
Physical exam: Focus on 3 questions
During a routine, thorough examination of the breasts and axillae, focus on the following issues:
Although cytology of the discharge can be performed at this time, the yield may be low.
As with a mass, the cause of the discharge must be determined even if cytology is benign.
During the physical examination, the gynecologist palpates a subareolar mass. A subsequent mammogram identifies only this single, subareolar lesion. Although mammography is always indicated in cases of nipple discharge, sonography can be a helpful addition, as it can identify a dilated duct with a filling defect.
This patient is found to have a benign intraductal papilloma, which is surgically removed.
CASE 4 Inflammation of the breast
P.D., 41, has had 3 full-term deliveries, the most recent one just 3 weeks ago in another city. She had no prenatal care during any of her pregnancies.
While breast-feeding her new infant, P.D. noticed that the upper outer quadrant of her right breast was inflamed. She also had low-grade fever. When she visited the emergency room, she was given oral dicloxacillin and sent home. She took the medication as prescribed for several days, but had no response.
Today she returns to the emergency room with a fever of 101°F. The area of inflammation has extended beyond the upper outer quadrant of the breast and is tender, with significant skin thickening and edema in the inflamed area, as well as redness and warmth. There is no pointing abscess and no purulent discharge. A culture of the breast milk is obtained and is normal, as is the contralateral breast.
P.D. is admitted to the hospital for intravenous antibiotics. Because there is concern about methicillin-resistant Staphylococcus aureus, she is started on intravenous vancomycin.
A breast surgeon called in to evaluate the patient concludes no abscess is present. The surgeon believes the clinical picture might be consistent with inflammatory breast cancer, which often involves extensive invasion of the dermal lymphatics by cancer.
What is the next step?
In a breast-feeding woman, mastitis is usually the cause of inflammation
Postpartum mastitis is a common problem, and would be the most likely diagnosis in a woman presenting with breast inflammation within several weeks of delivery. Staphylococcus aureus is the most common etiologic agent, although streptococci are sometimes involved. Women with postpartum mastitis usually present with a tender, warm, red section of the breast and may have systemic evidence of infection, including general malaise, fever, and leukocytosis. Cracked or irritated nipples are also common.
Treatment-resistant mastitis justifies intravenous therapy
Women who have puerperal mastitis but who do not respond to appropriate antibiotic therapy may require intravenous treatment. Since methicillin-resistant Staphylococcus aureus is a concern, intravenous vancomycin may be necessary.
Occasionally, puerperal mastitis progresses to a breast abscess, necessitating drainage in addition to antibiotics. There may be loculations that need to be broken up to ensure adequate drainage.
More sinister conditions can mark postpartum period
Because postpartum mastitis is relatively common, and postpartum breast cancer fairly uncommon, it is no surprise that the gynecologist suspected mastitis in this case. However, pregnancy-associated breast cancer—cancer that occurs during pregnancy or within the first year after delivery—affects between 1 in 3,000 and 1 in 10,000 pregnancies.11
Earlier reports suggested a dismal prognosis for pregnancy-associated breast cancer. Newer data suggest that, stage for stage, with all other parameters controlled for, there may be no significant differences in 5- and 10-year survival for pregnancy-associated breast cancer, compared with breast cancer in nongravid, non-postpartum women.11
Inflammatory carcinoma of the breast has a generally poor prognosis, whether or not it is related to pregnancy.
The patient undergoes mammography immediately after pumping the breasts. It shows prominent subcutaneous lymphatic vessels and thickened skin. A breast sonogram is performed to rule out an occult abscess, but none is identified.
A skin biopsy confirms the presence of inflammatory carcinoma, with dilated dermal lymphatic channels containing intralymphatic tumor emboli.
The author reports no relevant financial relationships.
1. Seltzer V. Cancer in women: prevention and early detection. J Women’s Hlth Gender-Based Med. 2000;9:483-488.
2. American Cancer Society. Breast cancer facts and figures, 2005-2006. Atlanta: ACS; 2006.
3. Hendrick RE, et al. Benefit of screening mammography in women aged 40 to 49: a new meta-analysis of randomized controlled trials. Monogr Natl Cancer Inst. 1997;22:87-92.
4. Bjurstam N, Bjorneld L, Duffy SW, et al. Gothenberg breast screening trial. Cancer. 1997;80:2091-2099.
5. Duffy SW, Tabar L, Chen HH, et al. The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties. Cancer. 2002;95:458-469.
6. Gundry KR, Berg WA. Treatment issues and core needle breast biopsy. Clinical context. Am J Roentgenol. 1998;171:41-49.
7. American College of Radiology. Breast Imaging Reporting and Data System (BI-RADS) Atlas, 4th ed. Reston, Va: ACR; 2003.
8. American College of Radiology ACR Practice Guideline for the Performance of Magnetic Resonance Imaging (MRI) of the Breast. Reston, Va: ACR; 2004:341-346.
9. Role of the obstetrician-gynecologist in the screening and diagnosis of breast masses. American College of Obstetricians and Gynecologists. Washington, DC: ACOG; 2006.
10. Seltzer V, Petrek J. The breast. In: Seltzer V, Pearse W, eds. Women’s Primary Health Care. New York: McGraw-Hill; 2000:793-823.
11. Petrek J, Seltzer V. Breast cancer in pregnant and postpartum women. J Obstet Gynaecol Can. 2003;25:944-950.
12. Liberman L, Morris EA, Dershaw DD, et al. MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol. 2003;180:901-910.
13. Harms SE, Flamig DP, Hesley KL, et al. MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. Radiology. 1993;187:493-501.
What’s the most common cause of death in women 40 to 44 years of age?
Answer: Breast cancer.1
What population has the highest death toll from breast cancer?
Answer: Women age 40 and older. Approximately 95% of new breast cancer cases and 97% of breast cancer deaths occur in women 40 and older.2
Why are many women in their 40s under-screened?
Answer: Because clinicians sometimes under-appreciate their risk.
Of course, the majority of breast cancer cases and deaths involve postmenopausal women. But this doesn’t mean younger women don’t warrant heightened scrutiny. This article presents 4 cases that focus on breast disease in women 40 to 49 years of age and the optimal workup for patients with suspicious findings. It includes recommendations on:
Digital mammography may aid in evaluation of dense breast tissue
Although early breast cancer may be more difficult to identify on mammography in premenopausal women because of their denser breast tissue, there are good data on the benefits of screening mammography for women in the 40- to 49-year-old age group,3,4 as well as for women age 50 and older.5 In addition, digital mammography is often helpful in women with radiographically dense breasts.
Screening vs diagnostic mammography
Women who have no complaints and no abnormal physical findings on self- or clinical examination typically undergo screening mammography. In typical cases, 2 views of each breast are obtained, and the radiologist often postpones reading the images until the end of the day, when they are scrutinized in batches.
In contrast, diagnostic mammography is performed when a possible problem arises, and several additional “coned-down” views may be needed. The radiologist interprets the study while the patient is still in the radiology office.
It is essential that gynecologists indicate on the mammography referral form whether they are requesting a diagnostic or screening mammogram. If it is a diagnostic mammogram, the reason and precise location of any suspicious areas need to be clearly communicated to the radiologist. In either case, the patient should be reminded to provide any previous images the radiologist does not already have.
I obtain routine annual screening mammography for my average-risk patients from age 40 onward, since more than 50,000 American women under age 50 are diagnosed with breast cancer each year.
CASE 1 Abnormal mammogram
S.H. is a healthy 43-year-old who had vaginal deliveries at ages 25 and 28 and has always used barrier contraception. She has no family history of cancer or high-risk factors for breast cancer. Her breast and pelvic examinations at the time of her routine gynecologic visit are normal. She has undergone annual mammography since she was 40 years old, but recently moved from another state and did not bring her mammograms with her.
She is sent for a screening mammogram, and 2 radiographic views of each breast are obtained. Upon review, the images are classified as Breast Imaging Reporting and Data Systems (BI-RADS) category 0, indicating that mammographic assessment is incomplete. The radiologist wants additional images of an area in the upper outer quadrant of the right breast, and wants to compare this study with the patient’s old films if they are available. S.H. returns the next day for the additional imaging, and the radiologist identifies an 8-mm area of suspicious calcifications in the right breast, reclassifying the mammogram as BI-RADS category 4.
The radiologist recommends a stereotactic biopsy, but S.H. wants your advice on whether to comply or proceed immediately to open biopsy.
What do you tell her?
Barely invasive biopsy
Stereotactic needle biopsy offers precise positioning in 3 dimensions without the lag time and scarring associated with open biopsies.In the case above, stereotactic biopsy is a good option, since it can usually be scheduled rapidly, does not require an operating room or anesthesia, is less expensive than open biopsy, and involves less scarring.6 If a patient’s lesion is clearly benign on stereotactic biopsy, she may be spared an open biopsy. If it is malignant, she can immediately begin to make treatment decisions.
Breast imaging categories
BI-RADS categories have standardized the reporting of mammograms and include the following7:
S.H. schedules a stereotactic biopsy for the following day in the radiologist’s office. Tissue diagnosis reveals an invasive ductal carcinoma, and the patient elects to undergo lumpectomy and radiation therapy.
CASE 2 Self-palpated lesion
L.J., 45, has no personal or family history of cancer and no high-risk factors, and she has undergone annual mammograms since the age of 40. Her last mammogram, which was negative, was 3 months ago.
Today L.J. reports that she felt a 1-cm lesion in the upper outer quadrant of her left breast during monthly breast self-examination. Although she is somewhat reassured by the normal mammogram 3 months earlier, she had been instructed by her gynecologist to call if she ever had any abnormal findings on breast self-examination.
Her gynecologist performs a thorough history and physical examination of the breasts and lymph nodes, confirming the presence of the lesion but no other abnormalities.
What is the next step?
Self-examination and imaging don’t always agree
It is vital that a diagnosis be made whenever a mass is present in the breast—even if the mammogram is normal—since 10% to 15% of women with breast cancer have normal mammograms.1
In this case, the first step is to review the prior mammogram. If no abnormality is found on the mammogram, the patient should undergo further imaging to ascertain whether the lesion appears benign or suspicious for malignancy.
However, even if all radiologic studies are normal, definitive diagnosis is crucial when a mass is present.
MRI may be useful when other imaging is inconclusive
In 2004, the American College of Radiology (ACR) published guidelines for breast MRI,8 which advise against using the modality for breast cancer screening in the general population of asymptomatic women because of the likelihood of false positives. However, MRI is recommended by the ACR in a wide range of situations, including those in which other imaging such as mammography or ultrasound has been inconclusive.
I encourage self-examination
Because 75% of women diagnosed with breast cancer lack major high-risk factors, all women should be screened, and I believe self-examination should be encouraged. Although data from randomized controlled trials of breast self-examination do not confirm a reduction in overall breast cancer mortality with the practice, it may lead to earlier detection in some women.9
While L.J. is in the office, the gynecologist telephones the radiologist and asks her to review the mammogram. The radiologist does so, comparing the latest films with prior mammograms, and calls back to report the absence of abnormal findings.
The patient is then sent for ultrasound of the breast, which does not reveal a cyst but does show some suspicious changes. After a breast MRI is consistent with malignancy, the lesion is biopsied and diagnosed as invasive lobular carcinoma.
Mammography isn’t perfect. Neither is magnetic resonance imaging (MRI). But both can be revealing in the right patients. MRI studies suggest it is better at imaging soft tissues and can detect lesions not visible on mammogram in 27% to 37% of patients.12,13
The downside: cost. Because MRI is 10 to 15 times more costly than mammography, it is usually limited to patients with suspicious findings or high risk.
Higher predictive value, biopsy still needed
Bluemke DA, Catsonis CA, Chen MH, et al. Magnetic resonance imaging of the breast prior to biopsy. JAMA. 2004;292:2735–2742.
A prospective multicenter study by the International Breast MR Consortium involved 821 women referred for breast biopsy at 14 university hospitals in North America and Europe. All women had BI-RADS category 4 or 5 mammographic evaluation and breast MRI prior to the biopsy, with imaging interpreted at each site without knowledge of the biopsy results.
Findings: MRI correctly identified cancer in 356 of 404 cancer cases, for a sensitivity of 88.1% (95% confidence interval [CI] 84.6–91.1). It also correctly ruled out cancer in 281 of 417 cases with benign findings, for a specificity of 67.7% (95% CI 62.7–71.9). The positive predictive value of MRI for 356 of 492 patients was 72.4% (95% CI 68.2–76.3), compared with 52.8% for mammography in 367 of 695 patients (95% CI 49.0–56.6).
Conclusion: Despite the higher predictive value of MRI, tissue sampling is still needed when suspicious findings are detected.
Annual MRI and mammography for women at high risk
Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study. Lancet. 2005;365:1769–1778.
This prospective, multicenter study compared mammography with contrast-enhanced MRI in 649 women aged 35 to 49 who had a strong family history of breast cancer or a high probability of BRCA1, BRCA2, or TP53 mutation. The women had annual screening with both modalities for 2 to 7 years.
Findings: Thirtyfive cancers were diagnosed—19 by contrast-enhanced MRI only, 6 by mammography only, and 8 by both, with 2 “interval” cases. Sensitivity for contrast-enhanced MRI was significantly higher than for mammography (77% vs 40%; 95% CI 60–90 vs 24–58); when both modalities were used, it was 94% (95% CI 81–99). The contrast in sensitivity between the 2 modalities was particularly sharp in women with BRCA1 mutations: 92% for MRI vs 23% for mammography (P=.004). However, specificity was higher for mammography (93% vs 81%; 95% CI 92–95 vs 80–83); when both mammography and MRI were used, specificity was 77% (95% CI 75–79).
Leach et al noted a high proportion of grade 3 cancers in this study, but the tumors were small and most women were node-negative.
Conclusion: Annual screening with both contrast-enhanced MRI and mammography would detect most cancers in high-risk women.
MRI is more cost-effective in women with BRCA1/2 mutations
Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006;295:2374–2384.
Using a computer model to simulate the life histories of individual BRCA1 and BRCA2 mutation carriers, Plevritis et al compared mammography and breast MRI for cancer screening, using published data to estimate the accuracy of the 2 modalities. Breast cancer survival was based on the Surveillance, Epidemiology, and End Results (SEER) database, whereas utilization rates and intervention costs were based on published data and Medicare payments for 2005.
Findings: For each quality-adjusted life-year (QALY) gained, the cost of annual MRI in addition to annual mammography ranged from less than $45,000 to more than $700,000, depending on the patient’s age and specific BRCA mutation. Compared with mammography alone, the cost of MRI for each QALY gained in women aged 35 to 54 years was $55,420 for BRCA1 mutation carriers, $130,695 for BRCA2 mutation carriers, and $98,454 for BRCA2 mutation carriers with mammographically dense breasts.
Conclusion: Breast MRI screening is more cost-effective in women with BRCA1 mutations. The cost-effectiveness of adding it to mammography also varies greatly by age.
CASE 3 Bloody nipple discharge
M.W. is a 48-year-old nulliparous woman who has noticed blood in her bra in the area of the right nipple several times during the past month. Her last mammogram, which was normal, was 1 year ago. Her history lacks any relevant problems other than the nipple discharge itself. Her menstrual periods are regular; the last one was 2 weeks earlier. Many years ago, she underwent a tubal ligation. She does not take any medications.
How should she be evaluated?
Nipple discharge is a common phenomenon, more so among women with benign problems (approximately 10%–15%) than in women with malignancies (approximately 3%).10
When taking a history from a woman with nipple discharge, ask about the color of the discharge; whether it is bilateral; whether it is spontaneous; and its frequency and duration.
Physical exam: Focus on 3 questions
During a routine, thorough examination of the breasts and axillae, focus on the following issues:
Although cytology of the discharge can be performed at this time, the yield may be low.
As with a mass, the cause of the discharge must be determined even if cytology is benign.
During the physical examination, the gynecologist palpates a subareolar mass. A subsequent mammogram identifies only this single, subareolar lesion. Although mammography is always indicated in cases of nipple discharge, sonography can be a helpful addition, as it can identify a dilated duct with a filling defect.
This patient is found to have a benign intraductal papilloma, which is surgically removed.
CASE 4 Inflammation of the breast
P.D., 41, has had 3 full-term deliveries, the most recent one just 3 weeks ago in another city. She had no prenatal care during any of her pregnancies.
While breast-feeding her new infant, P.D. noticed that the upper outer quadrant of her right breast was inflamed. She also had low-grade fever. When she visited the emergency room, she was given oral dicloxacillin and sent home. She took the medication as prescribed for several days, but had no response.
Today she returns to the emergency room with a fever of 101°F. The area of inflammation has extended beyond the upper outer quadrant of the breast and is tender, with significant skin thickening and edema in the inflamed area, as well as redness and warmth. There is no pointing abscess and no purulent discharge. A culture of the breast milk is obtained and is normal, as is the contralateral breast.
P.D. is admitted to the hospital for intravenous antibiotics. Because there is concern about methicillin-resistant Staphylococcus aureus, she is started on intravenous vancomycin.
A breast surgeon called in to evaluate the patient concludes no abscess is present. The surgeon believes the clinical picture might be consistent with inflammatory breast cancer, which often involves extensive invasion of the dermal lymphatics by cancer.
What is the next step?
In a breast-feeding woman, mastitis is usually the cause of inflammation
Postpartum mastitis is a common problem, and would be the most likely diagnosis in a woman presenting with breast inflammation within several weeks of delivery. Staphylococcus aureus is the most common etiologic agent, although streptococci are sometimes involved. Women with postpartum mastitis usually present with a tender, warm, red section of the breast and may have systemic evidence of infection, including general malaise, fever, and leukocytosis. Cracked or irritated nipples are also common.
Treatment-resistant mastitis justifies intravenous therapy
Women who have puerperal mastitis but who do not respond to appropriate antibiotic therapy may require intravenous treatment. Since methicillin-resistant Staphylococcus aureus is a concern, intravenous vancomycin may be necessary.
Occasionally, puerperal mastitis progresses to a breast abscess, necessitating drainage in addition to antibiotics. There may be loculations that need to be broken up to ensure adequate drainage.
More sinister conditions can mark postpartum period
Because postpartum mastitis is relatively common, and postpartum breast cancer fairly uncommon, it is no surprise that the gynecologist suspected mastitis in this case. However, pregnancy-associated breast cancer—cancer that occurs during pregnancy or within the first year after delivery—affects between 1 in 3,000 and 1 in 10,000 pregnancies.11
Earlier reports suggested a dismal prognosis for pregnancy-associated breast cancer. Newer data suggest that, stage for stage, with all other parameters controlled for, there may be no significant differences in 5- and 10-year survival for pregnancy-associated breast cancer, compared with breast cancer in nongravid, non-postpartum women.11
Inflammatory carcinoma of the breast has a generally poor prognosis, whether or not it is related to pregnancy.
The patient undergoes mammography immediately after pumping the breasts. It shows prominent subcutaneous lymphatic vessels and thickened skin. A breast sonogram is performed to rule out an occult abscess, but none is identified.
A skin biopsy confirms the presence of inflammatory carcinoma, with dilated dermal lymphatic channels containing intralymphatic tumor emboli.
The author reports no relevant financial relationships.
What’s the most common cause of death in women 40 to 44 years of age?
Answer: Breast cancer.1
What population has the highest death toll from breast cancer?
Answer: Women age 40 and older. Approximately 95% of new breast cancer cases and 97% of breast cancer deaths occur in women 40 and older.2
Why are many women in their 40s under-screened?
Answer: Because clinicians sometimes under-appreciate their risk.
Of course, the majority of breast cancer cases and deaths involve postmenopausal women. But this doesn’t mean younger women don’t warrant heightened scrutiny. This article presents 4 cases that focus on breast disease in women 40 to 49 years of age and the optimal workup for patients with suspicious findings. It includes recommendations on:
Digital mammography may aid in evaluation of dense breast tissue
Although early breast cancer may be more difficult to identify on mammography in premenopausal women because of their denser breast tissue, there are good data on the benefits of screening mammography for women in the 40- to 49-year-old age group,3,4 as well as for women age 50 and older.5 In addition, digital mammography is often helpful in women with radiographically dense breasts.
Screening vs diagnostic mammography
Women who have no complaints and no abnormal physical findings on self- or clinical examination typically undergo screening mammography. In typical cases, 2 views of each breast are obtained, and the radiologist often postpones reading the images until the end of the day, when they are scrutinized in batches.
In contrast, diagnostic mammography is performed when a possible problem arises, and several additional “coned-down” views may be needed. The radiologist interprets the study while the patient is still in the radiology office.
It is essential that gynecologists indicate on the mammography referral form whether they are requesting a diagnostic or screening mammogram. If it is a diagnostic mammogram, the reason and precise location of any suspicious areas need to be clearly communicated to the radiologist. In either case, the patient should be reminded to provide any previous images the radiologist does not already have.
I obtain routine annual screening mammography for my average-risk patients from age 40 onward, since more than 50,000 American women under age 50 are diagnosed with breast cancer each year.
CASE 1 Abnormal mammogram
S.H. is a healthy 43-year-old who had vaginal deliveries at ages 25 and 28 and has always used barrier contraception. She has no family history of cancer or high-risk factors for breast cancer. Her breast and pelvic examinations at the time of her routine gynecologic visit are normal. She has undergone annual mammography since she was 40 years old, but recently moved from another state and did not bring her mammograms with her.
She is sent for a screening mammogram, and 2 radiographic views of each breast are obtained. Upon review, the images are classified as Breast Imaging Reporting and Data Systems (BI-RADS) category 0, indicating that mammographic assessment is incomplete. The radiologist wants additional images of an area in the upper outer quadrant of the right breast, and wants to compare this study with the patient’s old films if they are available. S.H. returns the next day for the additional imaging, and the radiologist identifies an 8-mm area of suspicious calcifications in the right breast, reclassifying the mammogram as BI-RADS category 4.
The radiologist recommends a stereotactic biopsy, but S.H. wants your advice on whether to comply or proceed immediately to open biopsy.
What do you tell her?
Barely invasive biopsy
Stereotactic needle biopsy offers precise positioning in 3 dimensions without the lag time and scarring associated with open biopsies.In the case above, stereotactic biopsy is a good option, since it can usually be scheduled rapidly, does not require an operating room or anesthesia, is less expensive than open biopsy, and involves less scarring.6 If a patient’s lesion is clearly benign on stereotactic biopsy, she may be spared an open biopsy. If it is malignant, she can immediately begin to make treatment decisions.
Breast imaging categories
BI-RADS categories have standardized the reporting of mammograms and include the following7:
S.H. schedules a stereotactic biopsy for the following day in the radiologist’s office. Tissue diagnosis reveals an invasive ductal carcinoma, and the patient elects to undergo lumpectomy and radiation therapy.
CASE 2 Self-palpated lesion
L.J., 45, has no personal or family history of cancer and no high-risk factors, and she has undergone annual mammograms since the age of 40. Her last mammogram, which was negative, was 3 months ago.
Today L.J. reports that she felt a 1-cm lesion in the upper outer quadrant of her left breast during monthly breast self-examination. Although she is somewhat reassured by the normal mammogram 3 months earlier, she had been instructed by her gynecologist to call if she ever had any abnormal findings on breast self-examination.
Her gynecologist performs a thorough history and physical examination of the breasts and lymph nodes, confirming the presence of the lesion but no other abnormalities.
What is the next step?
Self-examination and imaging don’t always agree
It is vital that a diagnosis be made whenever a mass is present in the breast—even if the mammogram is normal—since 10% to 15% of women with breast cancer have normal mammograms.1
In this case, the first step is to review the prior mammogram. If no abnormality is found on the mammogram, the patient should undergo further imaging to ascertain whether the lesion appears benign or suspicious for malignancy.
However, even if all radiologic studies are normal, definitive diagnosis is crucial when a mass is present.
MRI may be useful when other imaging is inconclusive
In 2004, the American College of Radiology (ACR) published guidelines for breast MRI,8 which advise against using the modality for breast cancer screening in the general population of asymptomatic women because of the likelihood of false positives. However, MRI is recommended by the ACR in a wide range of situations, including those in which other imaging such as mammography or ultrasound has been inconclusive.
I encourage self-examination
Because 75% of women diagnosed with breast cancer lack major high-risk factors, all women should be screened, and I believe self-examination should be encouraged. Although data from randomized controlled trials of breast self-examination do not confirm a reduction in overall breast cancer mortality with the practice, it may lead to earlier detection in some women.9
While L.J. is in the office, the gynecologist telephones the radiologist and asks her to review the mammogram. The radiologist does so, comparing the latest films with prior mammograms, and calls back to report the absence of abnormal findings.
The patient is then sent for ultrasound of the breast, which does not reveal a cyst but does show some suspicious changes. After a breast MRI is consistent with malignancy, the lesion is biopsied and diagnosed as invasive lobular carcinoma.
Mammography isn’t perfect. Neither is magnetic resonance imaging (MRI). But both can be revealing in the right patients. MRI studies suggest it is better at imaging soft tissues and can detect lesions not visible on mammogram in 27% to 37% of patients.12,13
The downside: cost. Because MRI is 10 to 15 times more costly than mammography, it is usually limited to patients with suspicious findings or high risk.
Higher predictive value, biopsy still needed
Bluemke DA, Catsonis CA, Chen MH, et al. Magnetic resonance imaging of the breast prior to biopsy. JAMA. 2004;292:2735–2742.
A prospective multicenter study by the International Breast MR Consortium involved 821 women referred for breast biopsy at 14 university hospitals in North America and Europe. All women had BI-RADS category 4 or 5 mammographic evaluation and breast MRI prior to the biopsy, with imaging interpreted at each site without knowledge of the biopsy results.
Findings: MRI correctly identified cancer in 356 of 404 cancer cases, for a sensitivity of 88.1% (95% confidence interval [CI] 84.6–91.1). It also correctly ruled out cancer in 281 of 417 cases with benign findings, for a specificity of 67.7% (95% CI 62.7–71.9). The positive predictive value of MRI for 356 of 492 patients was 72.4% (95% CI 68.2–76.3), compared with 52.8% for mammography in 367 of 695 patients (95% CI 49.0–56.6).
Conclusion: Despite the higher predictive value of MRI, tissue sampling is still needed when suspicious findings are detected.
Annual MRI and mammography for women at high risk
Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study. Lancet. 2005;365:1769–1778.
This prospective, multicenter study compared mammography with contrast-enhanced MRI in 649 women aged 35 to 49 who had a strong family history of breast cancer or a high probability of BRCA1, BRCA2, or TP53 mutation. The women had annual screening with both modalities for 2 to 7 years.
Findings: Thirtyfive cancers were diagnosed—19 by contrast-enhanced MRI only, 6 by mammography only, and 8 by both, with 2 “interval” cases. Sensitivity for contrast-enhanced MRI was significantly higher than for mammography (77% vs 40%; 95% CI 60–90 vs 24–58); when both modalities were used, it was 94% (95% CI 81–99). The contrast in sensitivity between the 2 modalities was particularly sharp in women with BRCA1 mutations: 92% for MRI vs 23% for mammography (P=.004). However, specificity was higher for mammography (93% vs 81%; 95% CI 92–95 vs 80–83); when both mammography and MRI were used, specificity was 77% (95% CI 75–79).
Leach et al noted a high proportion of grade 3 cancers in this study, but the tumors were small and most women were node-negative.
Conclusion: Annual screening with both contrast-enhanced MRI and mammography would detect most cancers in high-risk women.
MRI is more cost-effective in women with BRCA1/2 mutations
Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006;295:2374–2384.
Using a computer model to simulate the life histories of individual BRCA1 and BRCA2 mutation carriers, Plevritis et al compared mammography and breast MRI for cancer screening, using published data to estimate the accuracy of the 2 modalities. Breast cancer survival was based on the Surveillance, Epidemiology, and End Results (SEER) database, whereas utilization rates and intervention costs were based on published data and Medicare payments for 2005.
Findings: For each quality-adjusted life-year (QALY) gained, the cost of annual MRI in addition to annual mammography ranged from less than $45,000 to more than $700,000, depending on the patient’s age and specific BRCA mutation. Compared with mammography alone, the cost of MRI for each QALY gained in women aged 35 to 54 years was $55,420 for BRCA1 mutation carriers, $130,695 for BRCA2 mutation carriers, and $98,454 for BRCA2 mutation carriers with mammographically dense breasts.
Conclusion: Breast MRI screening is more cost-effective in women with BRCA1 mutations. The cost-effectiveness of adding it to mammography also varies greatly by age.
CASE 3 Bloody nipple discharge
M.W. is a 48-year-old nulliparous woman who has noticed blood in her bra in the area of the right nipple several times during the past month. Her last mammogram, which was normal, was 1 year ago. Her history lacks any relevant problems other than the nipple discharge itself. Her menstrual periods are regular; the last one was 2 weeks earlier. Many years ago, she underwent a tubal ligation. She does not take any medications.
How should she be evaluated?
Nipple discharge is a common phenomenon, more so among women with benign problems (approximately 10%–15%) than in women with malignancies (approximately 3%).10
When taking a history from a woman with nipple discharge, ask about the color of the discharge; whether it is bilateral; whether it is spontaneous; and its frequency and duration.
Physical exam: Focus on 3 questions
During a routine, thorough examination of the breasts and axillae, focus on the following issues:
Although cytology of the discharge can be performed at this time, the yield may be low.
As with a mass, the cause of the discharge must be determined even if cytology is benign.
During the physical examination, the gynecologist palpates a subareolar mass. A subsequent mammogram identifies only this single, subareolar lesion. Although mammography is always indicated in cases of nipple discharge, sonography can be a helpful addition, as it can identify a dilated duct with a filling defect.
This patient is found to have a benign intraductal papilloma, which is surgically removed.
CASE 4 Inflammation of the breast
P.D., 41, has had 3 full-term deliveries, the most recent one just 3 weeks ago in another city. She had no prenatal care during any of her pregnancies.
While breast-feeding her new infant, P.D. noticed that the upper outer quadrant of her right breast was inflamed. She also had low-grade fever. When she visited the emergency room, she was given oral dicloxacillin and sent home. She took the medication as prescribed for several days, but had no response.
Today she returns to the emergency room with a fever of 101°F. The area of inflammation has extended beyond the upper outer quadrant of the breast and is tender, with significant skin thickening and edema in the inflamed area, as well as redness and warmth. There is no pointing abscess and no purulent discharge. A culture of the breast milk is obtained and is normal, as is the contralateral breast.
P.D. is admitted to the hospital for intravenous antibiotics. Because there is concern about methicillin-resistant Staphylococcus aureus, she is started on intravenous vancomycin.
A breast surgeon called in to evaluate the patient concludes no abscess is present. The surgeon believes the clinical picture might be consistent with inflammatory breast cancer, which often involves extensive invasion of the dermal lymphatics by cancer.
What is the next step?
In a breast-feeding woman, mastitis is usually the cause of inflammation
Postpartum mastitis is a common problem, and would be the most likely diagnosis in a woman presenting with breast inflammation within several weeks of delivery. Staphylococcus aureus is the most common etiologic agent, although streptococci are sometimes involved. Women with postpartum mastitis usually present with a tender, warm, red section of the breast and may have systemic evidence of infection, including general malaise, fever, and leukocytosis. Cracked or irritated nipples are also common.
Treatment-resistant mastitis justifies intravenous therapy
Women who have puerperal mastitis but who do not respond to appropriate antibiotic therapy may require intravenous treatment. Since methicillin-resistant Staphylococcus aureus is a concern, intravenous vancomycin may be necessary.
Occasionally, puerperal mastitis progresses to a breast abscess, necessitating drainage in addition to antibiotics. There may be loculations that need to be broken up to ensure adequate drainage.
More sinister conditions can mark postpartum period
Because postpartum mastitis is relatively common, and postpartum breast cancer fairly uncommon, it is no surprise that the gynecologist suspected mastitis in this case. However, pregnancy-associated breast cancer—cancer that occurs during pregnancy or within the first year after delivery—affects between 1 in 3,000 and 1 in 10,000 pregnancies.11
Earlier reports suggested a dismal prognosis for pregnancy-associated breast cancer. Newer data suggest that, stage for stage, with all other parameters controlled for, there may be no significant differences in 5- and 10-year survival for pregnancy-associated breast cancer, compared with breast cancer in nongravid, non-postpartum women.11
Inflammatory carcinoma of the breast has a generally poor prognosis, whether or not it is related to pregnancy.
The patient undergoes mammography immediately after pumping the breasts. It shows prominent subcutaneous lymphatic vessels and thickened skin. A breast sonogram is performed to rule out an occult abscess, but none is identified.
A skin biopsy confirms the presence of inflammatory carcinoma, with dilated dermal lymphatic channels containing intralymphatic tumor emboli.
The author reports no relevant financial relationships.
1. Seltzer V. Cancer in women: prevention and early detection. J Women’s Hlth Gender-Based Med. 2000;9:483-488.
2. American Cancer Society. Breast cancer facts and figures, 2005-2006. Atlanta: ACS; 2006.
3. Hendrick RE, et al. Benefit of screening mammography in women aged 40 to 49: a new meta-analysis of randomized controlled trials. Monogr Natl Cancer Inst. 1997;22:87-92.
4. Bjurstam N, Bjorneld L, Duffy SW, et al. Gothenberg breast screening trial. Cancer. 1997;80:2091-2099.
5. Duffy SW, Tabar L, Chen HH, et al. The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties. Cancer. 2002;95:458-469.
6. Gundry KR, Berg WA. Treatment issues and core needle breast biopsy. Clinical context. Am J Roentgenol. 1998;171:41-49.
7. American College of Radiology. Breast Imaging Reporting and Data System (BI-RADS) Atlas, 4th ed. Reston, Va: ACR; 2003.
8. American College of Radiology ACR Practice Guideline for the Performance of Magnetic Resonance Imaging (MRI) of the Breast. Reston, Va: ACR; 2004:341-346.
9. Role of the obstetrician-gynecologist in the screening and diagnosis of breast masses. American College of Obstetricians and Gynecologists. Washington, DC: ACOG; 2006.
10. Seltzer V, Petrek J. The breast. In: Seltzer V, Pearse W, eds. Women’s Primary Health Care. New York: McGraw-Hill; 2000:793-823.
11. Petrek J, Seltzer V. Breast cancer in pregnant and postpartum women. J Obstet Gynaecol Can. 2003;25:944-950.
12. Liberman L, Morris EA, Dershaw DD, et al. MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol. 2003;180:901-910.
13. Harms SE, Flamig DP, Hesley KL, et al. MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. Radiology. 1993;187:493-501.
1. Seltzer V. Cancer in women: prevention and early detection. J Women’s Hlth Gender-Based Med. 2000;9:483-488.
2. American Cancer Society. Breast cancer facts and figures, 2005-2006. Atlanta: ACS; 2006.
3. Hendrick RE, et al. Benefit of screening mammography in women aged 40 to 49: a new meta-analysis of randomized controlled trials. Monogr Natl Cancer Inst. 1997;22:87-92.
4. Bjurstam N, Bjorneld L, Duffy SW, et al. Gothenberg breast screening trial. Cancer. 1997;80:2091-2099.
5. Duffy SW, Tabar L, Chen HH, et al. The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties. Cancer. 2002;95:458-469.
6. Gundry KR, Berg WA. Treatment issues and core needle breast biopsy. Clinical context. Am J Roentgenol. 1998;171:41-49.
7. American College of Radiology. Breast Imaging Reporting and Data System (BI-RADS) Atlas, 4th ed. Reston, Va: ACR; 2003.
8. American College of Radiology ACR Practice Guideline for the Performance of Magnetic Resonance Imaging (MRI) of the Breast. Reston, Va: ACR; 2004:341-346.
9. Role of the obstetrician-gynecologist in the screening and diagnosis of breast masses. American College of Obstetricians and Gynecologists. Washington, DC: ACOG; 2006.
10. Seltzer V, Petrek J. The breast. In: Seltzer V, Pearse W, eds. Women’s Primary Health Care. New York: McGraw-Hill; 2000:793-823.
11. Petrek J, Seltzer V. Breast cancer in pregnant and postpartum women. J Obstet Gynaecol Can. 2003;25:944-950.
12. Liberman L, Morris EA, Dershaw DD, et al. MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol. 2003;180:901-910.
13. Harms SE, Flamig DP, Hesley KL, et al. MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. Radiology. 1993;187:493-501.
Interstim: An implantable device for implacable urinary symptoms
Sacral neuromodulation stimulation (SNS) offers a less invasive alternative treatment for a difficult challenge: how to improve quality of life for patients with refractory lower urinary/pelvic floor disorders. In the past, the options were limited to radical surgical procedures such as urinary diversion, augmentation cystoplasty, or cystectomy.
The neuromodulation technique has been used for treatment of other disorders such as deep brain stimulation for Parkinson’s disease and vagal nerve stimulation for epilepsy. SNS stimulates the sacral nerves to modulate the neural reflexes that influence the bladder sphincter and pelvic floor.
The implantable InterStim device is FDA approved for the treatment of both storage and release disorders:
This article discusses several clinical trials that investigated its effectiveness, indications, and adverse events.
InterStim: The backstory
What is InterStim?
InterStim is an implantable system comprising a lead with 4 electrodes, an extension cable, and a programmable impulse generator. Usually, the lead is implanted into the S3 sacral nerve root, and the impulse generator is placed in the upper buttock region.
FDA approval
SNS for lower urinary tract disorders has been under investigation in clinical trials since 1981 and in multicenter trials conducted during the late 1980s. In 1997, the sacral neuromodulation system, InterStim (Medtronic Corp, Minneapolis, Minn), was FDA approved for treatment of urge incontinence, and, in 1999, for treatment of urinary frequency and urinary retention.
For tough cases
This method of therapy has proven to be an alternative treatment for a difficult patient group—those in whom pharmacological and behavioral management have failed. Therefore, considerable interest continues in the development of this method of therapy.
The delicate balance of stimulation and inhibition
A review of the neuroanatomy helps to explain the possible underlying mechanism of the workings of SNS. In the human, stimulation of the parasympathetic system through the pelvic nerves (S2–S4) leads to bladder emptying, and stimulation of the sympathetic system through the hypogastric nerves (T10–L2) leads to inhibition of bladder emptying.
The pudendal nerve receives information from Onuf’s nucleus in the S2–S4 level and innervates the skeletal muscle of the pelvic floor/external urethral sphincter.
The contraction and relaxation of these muscles are integral to micturition and bladder storage. A physiologic coordination exists between the somatic and the autonomic nervous system; it is when this delicate balance of stimulation and inhibition is changed by disease states that problems of urinary urgency, urge incontinence, and urinary retention result. Two guarding reflexes also work to prevent incontinence:
Bladder afferent pathways are mediated by unmyelinated C fibers (which detect noxious stimuli and trigger voiding) and small myelinated A fibers (which detect bladder muscle tension or fullness). Pudendal afferent input can turn on voiding reflexes by suppressing the guarding reflex pathways, and pudendal afferent input can also turn off overactive voiding by blocking ascending sensory pathways.
Thus, stimulation of the sacral nerves through pudendal afferent signaling influences bladder storage and emptying. Sacral neuromodulation affects these mechanisms by stimulating the somatic afferent inhibition of sensory processing in the spinal cord.
Does SNS successfully treat unrelenting urgency–frequency?
EFFICACY AND SAFETY
Hassouna M, Siegel S, Nyeholt A, et al. Sacral neuromodulation in the treatment of urgency–frequency symptoms: a multicenter study on efficacy and safety. J Urol. 2000;163:1849–1854.
All patients in this small, prospective, multicenter randomized trial had refractory urinary urgency–frequency. They completed extensive urologic evaluation consisting of voiding diaries, urodynamic testing, physical examination, and symptom questionnaires. Of the 51 patients, 90% were female and 10% were male. All patients underwent an office-based percutaneous stimulation trial of 3 to 7 days, to determine response to sacral nerve modulation. As practice guidelines dictate, a successful trial was determined if 50% or more of any urinary symptoms were relieved.
The patients were randomly assigned to 2 groups: the control group (n=26) that received no SNS and the study group (n=25), which underwent InterStim implantation. At 6 months, urinary symptoms in all patients were reassessed by urodynamic testing, SF-36 health survey, and voiding diaries.
In the control group, patients’ voiding diaries, symptoms, and urodynamic testing results remained unchanged. In the treatment group, 56% of patients had a greater than 50% reduction in the number of voids (<8) per day, compared with the control group. The treatment group had a significant increase in average voided volume from 118 to 226 cc, and a reduced degree of urgency. The treatment was associated with improved quality of life measured using the SF-36 health survey.
At 6 months, stimulation was turned off in 23 of the 26 patients in the treatment group. (One had the InterStim system explanted, and 2 refused to have the device turned off due to fear of return of symptoms.) When stimulation was turned off, symptoms did return to baseline. At 12 months, when the stimulation was turned back on, patients regained improvement in their urinary indices, which remained statistically significant. At 24 months, only 21 patients were evaluated on all analyses. The researchers reported that 43% of patients had maintained either fewer than 7 voids per day or at least a 50% reduction in the number of daily voids.
Although this report looked at effectiveness in only 51 patients, it did utilize a randomization method. A larger cohort, of 196 patients, was studied in a retrospective and prospective trial conducted by Spinelli and colleagues.
SHORT- AND LONG-TERM EFFICACY
Spinelli M, Bertapelle F, Cappellano F, et al, on behalf of the GINS Group. Chronic sacral neuromodulation in patients with lower urinary tract symptoms: results from a national register. J Urol. 2001;166:541–545.
A national register was created in Italy to collect results from all centers that were performing sacral neuromodulation. The investigators analyzed a total of 196 patients (46 males and 150 females).
Retrospective analysis
A total of 93 (18 male and 75 female) of the 196 were included, and 61 of the 93 patients were available for assessment. Mean follow-up was 41 months.
Prospective analysis
A total of 103 patients (28 males and 75 females) were followed, using voiding diaries, number of incontinence episodes, residual urine volume, number of catheterizations, pad use, and pain symptoms. Assessments were performed before percutaneous nerve evaluation and at 3-month intervals for 1 year, and at 6-month intervals for up to 2 years.
Detrusor instability. In the prospective register, 42 patients had detrusor instability. Compared with baseline, the mean number of incontinence episodes declined from 5.4 to1.1 at 12 months; 75% of patients had fewer than 8 micturitions per day at 3 months and 84% had fewer than 8 micturitions per day at 6 months, and this rate remained stable at 12 and 18 months. At 3 months, 57% of the study population was dry; at 6 months, 65% compared with baseline. At 18 months, 43% of the patients were completely dry. Improved quality of life was found in the patients with detrusor instability.
Voiding disorders. Of 103 patients, 35 had voiding disorders. At 3 and 6 months, 67% had stopped catheterization and 13% were catheterizing only once per day. At 9 and 12 months, 50% were not catheterizing and 33% to 13% were catheterizing once per day; 67% were not catheterizing at 18 months. However, the remaining 33% of patients had fluctuating results.
Complications and adverse events. In patients followed prospectively, 15.5% required surgical revision of the InterStim system due to pain at the implantation or to cable connection site or wound problems such as hematoma or lead fracture. Complete removal was performed in 3.9%.
ADDITIONAL REFERENCES
- Leng WW, Chancellor MB. How sacral nerve stimulation neuromodulation works. Urol Clin N Am. 2005;32:11–18.
- Weil EHJ, Ruiz-Cerda JL, Eerdsmans PHA, et al. Sacral root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized clinical trial. Eur Urol. 2000;37:161–171.
Sacral neuromodulation stimulation (SNS) is a minimally invasive treatment for refractory urinary urge incontinence, urinary urgency–frequency alone or in combination, and urinary retention
The InterStim implantable system comprises a lead with 4 electrodes and an extension cable. Its programmable impulse generator, usually placed in the upper buttock region, sends mild electrical pulses to the sacral nerve
Stimulation of the parasympathetic system through the pelvic nerves (S2–S4) leads to bladder emptying
Stimulation of the sympathetic system through the hypogastric nerves (T10–L2) leads to inhibition of bladder emptying
The pudendal nerve receives information from Onuf’s nucleus in the S2–S4 level and innervates the skeletal muscle of the pelvic floor/external urethral sphincter. Contraction and relaxation of these muscles are integral to micturition and bladder storage
2 guarding reflexes prevent incontinence: 1) between the bladder and the smooth muscles of the urethra, which is mediated by the efferent pathways of the sympathetic system, and2) between the afferent nerves in the bladder and the efferent pathways in the pudendal nerve, leading to contraction of the skeletal component of the urethra
Bladder afferent pathways are mediated by unmyelinated C fibers that detect noxious stimuli and trigger voiding, and by small myelinated A fibers that detect bladder muscle tension or fullness
Pudendal afferent input can turn on voiding reflexes by suppressing the guarding reflex pathways, and turn off overactive voiding by blocking ascending sensory pathways
Fecal incontinence improved, with and without treatment
Leroi AM, Parc Y, Lehur PA, et al. Efficacy of sacral nerve stimulation for fecal incontinence. Results of a multicenter double-blind crossover study. Ann Surg. 2005;242:662–669.
In this randomized crossover trial, 24 patients with fecal incontinence at least once a week for 3 months received InterStim. Patients were randomized to have the device ON or OFF for 1 month, and in the opposite mode (OFF or ON) for the 2nd month. At the end of the study, patients were given the option of keeping the SNS ON or OFF. Patients and outcome assessors were blinded to treatment assignment. All patients completed the study.
Primary outcomes were number of weekly incontinence and urgency episodes and mean delay for postponing defecation measured with patient diaries; quality of life as measured by the Cleveland Clinic score; and manometric data.
The median frequency of fecal incontinence episodes was significantly decreased in the ON mode compared with the OFF mode. There was improvement in quality of life scores as well. There was no significant change in the frequency of urgency episodes, the delay in postponing defecation, or number of bowel movements per week. There was an increase in maximum anal resting pressure in the ON mode. There were no differences in any other manometric parameters between the 2 modes.
Although symptoms improved markedly during the ON crossover mode, there was also significant improvement in the OFF mode compared with baseline. The median frequency of fecal incontinence episodes decreased by 90% in the ON mode, but also decreased by 76% in the OFF mode. Also, 89% of patients reported improvement during the ON mode and 63% reported improvement during the OFF mode.
It is unclear if subjects were aware of which mode setting they were randomized to, or if there was significant placebo effect.
ADDITIONAL REFERENCES
- Rasmussen OO, Buntzen S, Sorensen M, Laurberg S, Christiansen J. Sacral nerve stimulation in fecal incontinence. Dis Colon Rectum. 2004;47:1158–1163.
Does the pudendal mini-stimulator improve detrusor overactivity?
Groen J, Amiel C, Rudd Bosch JLH. Chronic pudendal nerve neuromodulation in women with idiopathic refractory detrusor overactivity incontinence: results of a pilot study with a novel minimally invasive implantable mini-stimulator. Neurourol Urodynam. 2005;24:226–230.
The effectiveness of sacral neuromodulation has sparked innovations for other forms of neuromodulation besides the InterStim system. Utilizing the effects of stimulation on the pudendal afferents and in hopes of achieving similar results without central sacral stimulation, another type of neuromodulation has been developed: direct stimulation of the pudendal nerve by the Bion Device (Advanced Bionics Corp., Valencia, Calif). It is a self-contained, battery-powered mini-neurostimulator with integrated electrodes. It measures 28 x 3.3 mm and weighs 0.7 grams.
It is implanted in a minimally invasive fashion adjacent to the pudendal nerve at Alcock’s canal.
Other treatments had failed. This pilot study by Groen and colleagues evaluated short-term results of 6 women with refractory detrusor overactivity, in whom conservative and medical therapy and various forms of neuromodulation were unsuccessful, and who had positive percutaneous pudendal nerve screening tests.
Voiding–incontinence diaries, cystometrics, and the SF-36 quality-of-life health survey were measured. Women were followed for 6 months with the device ON, and for an additional 2 weeks with the device OFF.
Higher bladder volume remained better or returned to baseline
At the end of the 6-month ON period, the number of incontinence episodes per day, number of pads used per day, and leakage severity index decreased significantly compared with baseline (P<.05 for all). Cystometric comparisons revealed a higher bladder volume at the first involuntary detrusor contraction (P<.05). These values returned toward baseline when the device was turned OFF, although in most cases, still remained better than baseline.
There were no statistically significant changes in the 8 domains of the SF-36 survey, likely due to the small number of patients.
ADDITIONAL REFERENCES
- Bosch JLHR. The Bion Device: a minimally invasive implantable ministimulator for pudendal nerve neuromodulation in patients with detrusor overactivity incontinence. Urol Clin N Am. 2005;32:109–112.
- Daneshgari F. Applications of neuromodulation of the lower urinary tract in female urology. Int Braz J Urol. 2006;32:262–272.
- Spinelli M, Malaguti S, Giardiello G, et al. A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: description of the method and preliminary data. Neurourol Urodynam. 2005;24:305–309.
Sacral neuromodulation stimulation (SNS) offers a less invasive alternative treatment for a difficult challenge: how to improve quality of life for patients with refractory lower urinary/pelvic floor disorders. In the past, the options were limited to radical surgical procedures such as urinary diversion, augmentation cystoplasty, or cystectomy.
The neuromodulation technique has been used for treatment of other disorders such as deep brain stimulation for Parkinson’s disease and vagal nerve stimulation for epilepsy. SNS stimulates the sacral nerves to modulate the neural reflexes that influence the bladder sphincter and pelvic floor.
The implantable InterStim device is FDA approved for the treatment of both storage and release disorders:
This article discusses several clinical trials that investigated its effectiveness, indications, and adverse events.
InterStim: The backstory
What is InterStim?
InterStim is an implantable system comprising a lead with 4 electrodes, an extension cable, and a programmable impulse generator. Usually, the lead is implanted into the S3 sacral nerve root, and the impulse generator is placed in the upper buttock region.
FDA approval
SNS for lower urinary tract disorders has been under investigation in clinical trials since 1981 and in multicenter trials conducted during the late 1980s. In 1997, the sacral neuromodulation system, InterStim (Medtronic Corp, Minneapolis, Minn), was FDA approved for treatment of urge incontinence, and, in 1999, for treatment of urinary frequency and urinary retention.
For tough cases
This method of therapy has proven to be an alternative treatment for a difficult patient group—those in whom pharmacological and behavioral management have failed. Therefore, considerable interest continues in the development of this method of therapy.
The delicate balance of stimulation and inhibition
A review of the neuroanatomy helps to explain the possible underlying mechanism of the workings of SNS. In the human, stimulation of the parasympathetic system through the pelvic nerves (S2–S4) leads to bladder emptying, and stimulation of the sympathetic system through the hypogastric nerves (T10–L2) leads to inhibition of bladder emptying.
The pudendal nerve receives information from Onuf’s nucleus in the S2–S4 level and innervates the skeletal muscle of the pelvic floor/external urethral sphincter.
The contraction and relaxation of these muscles are integral to micturition and bladder storage. A physiologic coordination exists between the somatic and the autonomic nervous system; it is when this delicate balance of stimulation and inhibition is changed by disease states that problems of urinary urgency, urge incontinence, and urinary retention result. Two guarding reflexes also work to prevent incontinence:
Bladder afferent pathways are mediated by unmyelinated C fibers (which detect noxious stimuli and trigger voiding) and small myelinated A fibers (which detect bladder muscle tension or fullness). Pudendal afferent input can turn on voiding reflexes by suppressing the guarding reflex pathways, and pudendal afferent input can also turn off overactive voiding by blocking ascending sensory pathways.
Thus, stimulation of the sacral nerves through pudendal afferent signaling influences bladder storage and emptying. Sacral neuromodulation affects these mechanisms by stimulating the somatic afferent inhibition of sensory processing in the spinal cord.
Does SNS successfully treat unrelenting urgency–frequency?
EFFICACY AND SAFETY
Hassouna M, Siegel S, Nyeholt A, et al. Sacral neuromodulation in the treatment of urgency–frequency symptoms: a multicenter study on efficacy and safety. J Urol. 2000;163:1849–1854.
All patients in this small, prospective, multicenter randomized trial had refractory urinary urgency–frequency. They completed extensive urologic evaluation consisting of voiding diaries, urodynamic testing, physical examination, and symptom questionnaires. Of the 51 patients, 90% were female and 10% were male. All patients underwent an office-based percutaneous stimulation trial of 3 to 7 days, to determine response to sacral nerve modulation. As practice guidelines dictate, a successful trial was determined if 50% or more of any urinary symptoms were relieved.
The patients were randomly assigned to 2 groups: the control group (n=26) that received no SNS and the study group (n=25), which underwent InterStim implantation. At 6 months, urinary symptoms in all patients were reassessed by urodynamic testing, SF-36 health survey, and voiding diaries.
In the control group, patients’ voiding diaries, symptoms, and urodynamic testing results remained unchanged. In the treatment group, 56% of patients had a greater than 50% reduction in the number of voids (<8) per day, compared with the control group. The treatment group had a significant increase in average voided volume from 118 to 226 cc, and a reduced degree of urgency. The treatment was associated with improved quality of life measured using the SF-36 health survey.
At 6 months, stimulation was turned off in 23 of the 26 patients in the treatment group. (One had the InterStim system explanted, and 2 refused to have the device turned off due to fear of return of symptoms.) When stimulation was turned off, symptoms did return to baseline. At 12 months, when the stimulation was turned back on, patients regained improvement in their urinary indices, which remained statistically significant. At 24 months, only 21 patients were evaluated on all analyses. The researchers reported that 43% of patients had maintained either fewer than 7 voids per day or at least a 50% reduction in the number of daily voids.
Although this report looked at effectiveness in only 51 patients, it did utilize a randomization method. A larger cohort, of 196 patients, was studied in a retrospective and prospective trial conducted by Spinelli and colleagues.
SHORT- AND LONG-TERM EFFICACY
Spinelli M, Bertapelle F, Cappellano F, et al, on behalf of the GINS Group. Chronic sacral neuromodulation in patients with lower urinary tract symptoms: results from a national register. J Urol. 2001;166:541–545.
A national register was created in Italy to collect results from all centers that were performing sacral neuromodulation. The investigators analyzed a total of 196 patients (46 males and 150 females).
Retrospective analysis
A total of 93 (18 male and 75 female) of the 196 were included, and 61 of the 93 patients were available for assessment. Mean follow-up was 41 months.
Prospective analysis
A total of 103 patients (28 males and 75 females) were followed, using voiding diaries, number of incontinence episodes, residual urine volume, number of catheterizations, pad use, and pain symptoms. Assessments were performed before percutaneous nerve evaluation and at 3-month intervals for 1 year, and at 6-month intervals for up to 2 years.
Detrusor instability. In the prospective register, 42 patients had detrusor instability. Compared with baseline, the mean number of incontinence episodes declined from 5.4 to1.1 at 12 months; 75% of patients had fewer than 8 micturitions per day at 3 months and 84% had fewer than 8 micturitions per day at 6 months, and this rate remained stable at 12 and 18 months. At 3 months, 57% of the study population was dry; at 6 months, 65% compared with baseline. At 18 months, 43% of the patients were completely dry. Improved quality of life was found in the patients with detrusor instability.
Voiding disorders. Of 103 patients, 35 had voiding disorders. At 3 and 6 months, 67% had stopped catheterization and 13% were catheterizing only once per day. At 9 and 12 months, 50% were not catheterizing and 33% to 13% were catheterizing once per day; 67% were not catheterizing at 18 months. However, the remaining 33% of patients had fluctuating results.
Complications and adverse events. In patients followed prospectively, 15.5% required surgical revision of the InterStim system due to pain at the implantation or to cable connection site or wound problems such as hematoma or lead fracture. Complete removal was performed in 3.9%.
ADDITIONAL REFERENCES
- Leng WW, Chancellor MB. How sacral nerve stimulation neuromodulation works. Urol Clin N Am. 2005;32:11–18.
- Weil EHJ, Ruiz-Cerda JL, Eerdsmans PHA, et al. Sacral root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized clinical trial. Eur Urol. 2000;37:161–171.
Sacral neuromodulation stimulation (SNS) is a minimally invasive treatment for refractory urinary urge incontinence, urinary urgency–frequency alone or in combination, and urinary retention
The InterStim implantable system comprises a lead with 4 electrodes and an extension cable. Its programmable impulse generator, usually placed in the upper buttock region, sends mild electrical pulses to the sacral nerve
Stimulation of the parasympathetic system through the pelvic nerves (S2–S4) leads to bladder emptying
Stimulation of the sympathetic system through the hypogastric nerves (T10–L2) leads to inhibition of bladder emptying
The pudendal nerve receives information from Onuf’s nucleus in the S2–S4 level and innervates the skeletal muscle of the pelvic floor/external urethral sphincter. Contraction and relaxation of these muscles are integral to micturition and bladder storage
2 guarding reflexes prevent incontinence: 1) between the bladder and the smooth muscles of the urethra, which is mediated by the efferent pathways of the sympathetic system, and2) between the afferent nerves in the bladder and the efferent pathways in the pudendal nerve, leading to contraction of the skeletal component of the urethra
Bladder afferent pathways are mediated by unmyelinated C fibers that detect noxious stimuli and trigger voiding, and by small myelinated A fibers that detect bladder muscle tension or fullness
Pudendal afferent input can turn on voiding reflexes by suppressing the guarding reflex pathways, and turn off overactive voiding by blocking ascending sensory pathways
Fecal incontinence improved, with and without treatment
Leroi AM, Parc Y, Lehur PA, et al. Efficacy of sacral nerve stimulation for fecal incontinence. Results of a multicenter double-blind crossover study. Ann Surg. 2005;242:662–669.
In this randomized crossover trial, 24 patients with fecal incontinence at least once a week for 3 months received InterStim. Patients were randomized to have the device ON or OFF for 1 month, and in the opposite mode (OFF or ON) for the 2nd month. At the end of the study, patients were given the option of keeping the SNS ON or OFF. Patients and outcome assessors were blinded to treatment assignment. All patients completed the study.
Primary outcomes were number of weekly incontinence and urgency episodes and mean delay for postponing defecation measured with patient diaries; quality of life as measured by the Cleveland Clinic score; and manometric data.
The median frequency of fecal incontinence episodes was significantly decreased in the ON mode compared with the OFF mode. There was improvement in quality of life scores as well. There was no significant change in the frequency of urgency episodes, the delay in postponing defecation, or number of bowel movements per week. There was an increase in maximum anal resting pressure in the ON mode. There were no differences in any other manometric parameters between the 2 modes.
Although symptoms improved markedly during the ON crossover mode, there was also significant improvement in the OFF mode compared with baseline. The median frequency of fecal incontinence episodes decreased by 90% in the ON mode, but also decreased by 76% in the OFF mode. Also, 89% of patients reported improvement during the ON mode and 63% reported improvement during the OFF mode.
It is unclear if subjects were aware of which mode setting they were randomized to, or if there was significant placebo effect.
ADDITIONAL REFERENCES
- Rasmussen OO, Buntzen S, Sorensen M, Laurberg S, Christiansen J. Sacral nerve stimulation in fecal incontinence. Dis Colon Rectum. 2004;47:1158–1163.
Does the pudendal mini-stimulator improve detrusor overactivity?
Groen J, Amiel C, Rudd Bosch JLH. Chronic pudendal nerve neuromodulation in women with idiopathic refractory detrusor overactivity incontinence: results of a pilot study with a novel minimally invasive implantable mini-stimulator. Neurourol Urodynam. 2005;24:226–230.
The effectiveness of sacral neuromodulation has sparked innovations for other forms of neuromodulation besides the InterStim system. Utilizing the effects of stimulation on the pudendal afferents and in hopes of achieving similar results without central sacral stimulation, another type of neuromodulation has been developed: direct stimulation of the pudendal nerve by the Bion Device (Advanced Bionics Corp., Valencia, Calif). It is a self-contained, battery-powered mini-neurostimulator with integrated electrodes. It measures 28 x 3.3 mm and weighs 0.7 grams.
It is implanted in a minimally invasive fashion adjacent to the pudendal nerve at Alcock’s canal.
Other treatments had failed. This pilot study by Groen and colleagues evaluated short-term results of 6 women with refractory detrusor overactivity, in whom conservative and medical therapy and various forms of neuromodulation were unsuccessful, and who had positive percutaneous pudendal nerve screening tests.
Voiding–incontinence diaries, cystometrics, and the SF-36 quality-of-life health survey were measured. Women were followed for 6 months with the device ON, and for an additional 2 weeks with the device OFF.
Higher bladder volume remained better or returned to baseline
At the end of the 6-month ON period, the number of incontinence episodes per day, number of pads used per day, and leakage severity index decreased significantly compared with baseline (P<.05 for all). Cystometric comparisons revealed a higher bladder volume at the first involuntary detrusor contraction (P<.05). These values returned toward baseline when the device was turned OFF, although in most cases, still remained better than baseline.
There were no statistically significant changes in the 8 domains of the SF-36 survey, likely due to the small number of patients.
ADDITIONAL REFERENCES
- Bosch JLHR. The Bion Device: a minimally invasive implantable ministimulator for pudendal nerve neuromodulation in patients with detrusor overactivity incontinence. Urol Clin N Am. 2005;32:109–112.
- Daneshgari F. Applications of neuromodulation of the lower urinary tract in female urology. Int Braz J Urol. 2006;32:262–272.
- Spinelli M, Malaguti S, Giardiello G, et al. A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: description of the method and preliminary data. Neurourol Urodynam. 2005;24:305–309.
Sacral neuromodulation stimulation (SNS) offers a less invasive alternative treatment for a difficult challenge: how to improve quality of life for patients with refractory lower urinary/pelvic floor disorders. In the past, the options were limited to radical surgical procedures such as urinary diversion, augmentation cystoplasty, or cystectomy.
The neuromodulation technique has been used for treatment of other disorders such as deep brain stimulation for Parkinson’s disease and vagal nerve stimulation for epilepsy. SNS stimulates the sacral nerves to modulate the neural reflexes that influence the bladder sphincter and pelvic floor.
The implantable InterStim device is FDA approved for the treatment of both storage and release disorders:
This article discusses several clinical trials that investigated its effectiveness, indications, and adverse events.
InterStim: The backstory
What is InterStim?
InterStim is an implantable system comprising a lead with 4 electrodes, an extension cable, and a programmable impulse generator. Usually, the lead is implanted into the S3 sacral nerve root, and the impulse generator is placed in the upper buttock region.
FDA approval
SNS for lower urinary tract disorders has been under investigation in clinical trials since 1981 and in multicenter trials conducted during the late 1980s. In 1997, the sacral neuromodulation system, InterStim (Medtronic Corp, Minneapolis, Minn), was FDA approved for treatment of urge incontinence, and, in 1999, for treatment of urinary frequency and urinary retention.
For tough cases
This method of therapy has proven to be an alternative treatment for a difficult patient group—those in whom pharmacological and behavioral management have failed. Therefore, considerable interest continues in the development of this method of therapy.
The delicate balance of stimulation and inhibition
A review of the neuroanatomy helps to explain the possible underlying mechanism of the workings of SNS. In the human, stimulation of the parasympathetic system through the pelvic nerves (S2–S4) leads to bladder emptying, and stimulation of the sympathetic system through the hypogastric nerves (T10–L2) leads to inhibition of bladder emptying.
The pudendal nerve receives information from Onuf’s nucleus in the S2–S4 level and innervates the skeletal muscle of the pelvic floor/external urethral sphincter.
The contraction and relaxation of these muscles are integral to micturition and bladder storage. A physiologic coordination exists between the somatic and the autonomic nervous system; it is when this delicate balance of stimulation and inhibition is changed by disease states that problems of urinary urgency, urge incontinence, and urinary retention result. Two guarding reflexes also work to prevent incontinence:
Bladder afferent pathways are mediated by unmyelinated C fibers (which detect noxious stimuli and trigger voiding) and small myelinated A fibers (which detect bladder muscle tension or fullness). Pudendal afferent input can turn on voiding reflexes by suppressing the guarding reflex pathways, and pudendal afferent input can also turn off overactive voiding by blocking ascending sensory pathways.
Thus, stimulation of the sacral nerves through pudendal afferent signaling influences bladder storage and emptying. Sacral neuromodulation affects these mechanisms by stimulating the somatic afferent inhibition of sensory processing in the spinal cord.
Does SNS successfully treat unrelenting urgency–frequency?
EFFICACY AND SAFETY
Hassouna M, Siegel S, Nyeholt A, et al. Sacral neuromodulation in the treatment of urgency–frequency symptoms: a multicenter study on efficacy and safety. J Urol. 2000;163:1849–1854.
All patients in this small, prospective, multicenter randomized trial had refractory urinary urgency–frequency. They completed extensive urologic evaluation consisting of voiding diaries, urodynamic testing, physical examination, and symptom questionnaires. Of the 51 patients, 90% were female and 10% were male. All patients underwent an office-based percutaneous stimulation trial of 3 to 7 days, to determine response to sacral nerve modulation. As practice guidelines dictate, a successful trial was determined if 50% or more of any urinary symptoms were relieved.
The patients were randomly assigned to 2 groups: the control group (n=26) that received no SNS and the study group (n=25), which underwent InterStim implantation. At 6 months, urinary symptoms in all patients were reassessed by urodynamic testing, SF-36 health survey, and voiding diaries.
In the control group, patients’ voiding diaries, symptoms, and urodynamic testing results remained unchanged. In the treatment group, 56% of patients had a greater than 50% reduction in the number of voids (<8) per day, compared with the control group. The treatment group had a significant increase in average voided volume from 118 to 226 cc, and a reduced degree of urgency. The treatment was associated with improved quality of life measured using the SF-36 health survey.
At 6 months, stimulation was turned off in 23 of the 26 patients in the treatment group. (One had the InterStim system explanted, and 2 refused to have the device turned off due to fear of return of symptoms.) When stimulation was turned off, symptoms did return to baseline. At 12 months, when the stimulation was turned back on, patients regained improvement in their urinary indices, which remained statistically significant. At 24 months, only 21 patients were evaluated on all analyses. The researchers reported that 43% of patients had maintained either fewer than 7 voids per day or at least a 50% reduction in the number of daily voids.
Although this report looked at effectiveness in only 51 patients, it did utilize a randomization method. A larger cohort, of 196 patients, was studied in a retrospective and prospective trial conducted by Spinelli and colleagues.
SHORT- AND LONG-TERM EFFICACY
Spinelli M, Bertapelle F, Cappellano F, et al, on behalf of the GINS Group. Chronic sacral neuromodulation in patients with lower urinary tract symptoms: results from a national register. J Urol. 2001;166:541–545.
A national register was created in Italy to collect results from all centers that were performing sacral neuromodulation. The investigators analyzed a total of 196 patients (46 males and 150 females).
Retrospective analysis
A total of 93 (18 male and 75 female) of the 196 were included, and 61 of the 93 patients were available for assessment. Mean follow-up was 41 months.
Prospective analysis
A total of 103 patients (28 males and 75 females) were followed, using voiding diaries, number of incontinence episodes, residual urine volume, number of catheterizations, pad use, and pain symptoms. Assessments were performed before percutaneous nerve evaluation and at 3-month intervals for 1 year, and at 6-month intervals for up to 2 years.
Detrusor instability. In the prospective register, 42 patients had detrusor instability. Compared with baseline, the mean number of incontinence episodes declined from 5.4 to1.1 at 12 months; 75% of patients had fewer than 8 micturitions per day at 3 months and 84% had fewer than 8 micturitions per day at 6 months, and this rate remained stable at 12 and 18 months. At 3 months, 57% of the study population was dry; at 6 months, 65% compared with baseline. At 18 months, 43% of the patients were completely dry. Improved quality of life was found in the patients with detrusor instability.
Voiding disorders. Of 103 patients, 35 had voiding disorders. At 3 and 6 months, 67% had stopped catheterization and 13% were catheterizing only once per day. At 9 and 12 months, 50% were not catheterizing and 33% to 13% were catheterizing once per day; 67% were not catheterizing at 18 months. However, the remaining 33% of patients had fluctuating results.
Complications and adverse events. In patients followed prospectively, 15.5% required surgical revision of the InterStim system due to pain at the implantation or to cable connection site or wound problems such as hematoma or lead fracture. Complete removal was performed in 3.9%.
ADDITIONAL REFERENCES
- Leng WW, Chancellor MB. How sacral nerve stimulation neuromodulation works. Urol Clin N Am. 2005;32:11–18.
- Weil EHJ, Ruiz-Cerda JL, Eerdsmans PHA, et al. Sacral root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized clinical trial. Eur Urol. 2000;37:161–171.
Sacral neuromodulation stimulation (SNS) is a minimally invasive treatment for refractory urinary urge incontinence, urinary urgency–frequency alone or in combination, and urinary retention
The InterStim implantable system comprises a lead with 4 electrodes and an extension cable. Its programmable impulse generator, usually placed in the upper buttock region, sends mild electrical pulses to the sacral nerve
Stimulation of the parasympathetic system through the pelvic nerves (S2–S4) leads to bladder emptying
Stimulation of the sympathetic system through the hypogastric nerves (T10–L2) leads to inhibition of bladder emptying
The pudendal nerve receives information from Onuf’s nucleus in the S2–S4 level and innervates the skeletal muscle of the pelvic floor/external urethral sphincter. Contraction and relaxation of these muscles are integral to micturition and bladder storage
2 guarding reflexes prevent incontinence: 1) between the bladder and the smooth muscles of the urethra, which is mediated by the efferent pathways of the sympathetic system, and2) between the afferent nerves in the bladder and the efferent pathways in the pudendal nerve, leading to contraction of the skeletal component of the urethra
Bladder afferent pathways are mediated by unmyelinated C fibers that detect noxious stimuli and trigger voiding, and by small myelinated A fibers that detect bladder muscle tension or fullness
Pudendal afferent input can turn on voiding reflexes by suppressing the guarding reflex pathways, and turn off overactive voiding by blocking ascending sensory pathways
Fecal incontinence improved, with and without treatment
Leroi AM, Parc Y, Lehur PA, et al. Efficacy of sacral nerve stimulation for fecal incontinence. Results of a multicenter double-blind crossover study. Ann Surg. 2005;242:662–669.
In this randomized crossover trial, 24 patients with fecal incontinence at least once a week for 3 months received InterStim. Patients were randomized to have the device ON or OFF for 1 month, and in the opposite mode (OFF or ON) for the 2nd month. At the end of the study, patients were given the option of keeping the SNS ON or OFF. Patients and outcome assessors were blinded to treatment assignment. All patients completed the study.
Primary outcomes were number of weekly incontinence and urgency episodes and mean delay for postponing defecation measured with patient diaries; quality of life as measured by the Cleveland Clinic score; and manometric data.
The median frequency of fecal incontinence episodes was significantly decreased in the ON mode compared with the OFF mode. There was improvement in quality of life scores as well. There was no significant change in the frequency of urgency episodes, the delay in postponing defecation, or number of bowel movements per week. There was an increase in maximum anal resting pressure in the ON mode. There were no differences in any other manometric parameters between the 2 modes.
Although symptoms improved markedly during the ON crossover mode, there was also significant improvement in the OFF mode compared with baseline. The median frequency of fecal incontinence episodes decreased by 90% in the ON mode, but also decreased by 76% in the OFF mode. Also, 89% of patients reported improvement during the ON mode and 63% reported improvement during the OFF mode.
It is unclear if subjects were aware of which mode setting they were randomized to, or if there was significant placebo effect.
ADDITIONAL REFERENCES
- Rasmussen OO, Buntzen S, Sorensen M, Laurberg S, Christiansen J. Sacral nerve stimulation in fecal incontinence. Dis Colon Rectum. 2004;47:1158–1163.
Does the pudendal mini-stimulator improve detrusor overactivity?
Groen J, Amiel C, Rudd Bosch JLH. Chronic pudendal nerve neuromodulation in women with idiopathic refractory detrusor overactivity incontinence: results of a pilot study with a novel minimally invasive implantable mini-stimulator. Neurourol Urodynam. 2005;24:226–230.
The effectiveness of sacral neuromodulation has sparked innovations for other forms of neuromodulation besides the InterStim system. Utilizing the effects of stimulation on the pudendal afferents and in hopes of achieving similar results without central sacral stimulation, another type of neuromodulation has been developed: direct stimulation of the pudendal nerve by the Bion Device (Advanced Bionics Corp., Valencia, Calif). It is a self-contained, battery-powered mini-neurostimulator with integrated electrodes. It measures 28 x 3.3 mm and weighs 0.7 grams.
It is implanted in a minimally invasive fashion adjacent to the pudendal nerve at Alcock’s canal.
Other treatments had failed. This pilot study by Groen and colleagues evaluated short-term results of 6 women with refractory detrusor overactivity, in whom conservative and medical therapy and various forms of neuromodulation were unsuccessful, and who had positive percutaneous pudendal nerve screening tests.
Voiding–incontinence diaries, cystometrics, and the SF-36 quality-of-life health survey were measured. Women were followed for 6 months with the device ON, and for an additional 2 weeks with the device OFF.
Higher bladder volume remained better or returned to baseline
At the end of the 6-month ON period, the number of incontinence episodes per day, number of pads used per day, and leakage severity index decreased significantly compared with baseline (P<.05 for all). Cystometric comparisons revealed a higher bladder volume at the first involuntary detrusor contraction (P<.05). These values returned toward baseline when the device was turned OFF, although in most cases, still remained better than baseline.
There were no statistically significant changes in the 8 domains of the SF-36 survey, likely due to the small number of patients.
ADDITIONAL REFERENCES
- Bosch JLHR. The Bion Device: a minimally invasive implantable ministimulator for pudendal nerve neuromodulation in patients with detrusor overactivity incontinence. Urol Clin N Am. 2005;32:109–112.
- Daneshgari F. Applications of neuromodulation of the lower urinary tract in female urology. Int Braz J Urol. 2006;32:262–272.
- Spinelli M, Malaguti S, Giardiello G, et al. A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: description of the method and preliminary data. Neurourol Urodynam. 2005;24:305–309.
Coming soon to an OR near you!
What will the operating room of the future look like? Will it be a specialty-specific facility or a generic OR? Our Symposium panelists, each a primary investigator in an “OR of the Future” project at his own institution, share their ideas of what the future holds, from getting clutter off the floor and onto the ceiling, to integrating patient information, imaging, and robotic systems.
Panelists also share their visions of what the OR may look like in 25 years and what obstacles need to be overcome to make the futuristic vision a reality. Robotics, smart displays, information management and integration, and image-guided surgery may become as common as the stapler and the scalpel.
Dr. Rattner
The making of the “OR of the Future”
PARK: It’s been said that the operating room of the future means that we take the clutter off the floor and put it on the ceiling, but we need to have a much broader view.
“OR of the Future” embodies a vision of improved patient safety and outcomes—from evaluating and assimilating existing technologies, to identifying technologies that need to be developed or brought in, to integrating the technologies that will get us there.
SANDBERG: The “OR of the Future” is also about therapeutic effectiveness for our patients and organizational effectiveness for the hospital.
The OR of the future is a concept through which a big organization such as an academic hospital can foster innovative projects. It can designate a place within its own organization that’s politically, financially, and physically separate from the main workflow and objectives, where the hospital can test processes and technologies.
“Wall of Knowledge”
A matrix of real-time screens
This operating room at Memorial Sloan-Kettering Cancer Center is one of 21 that employ the “Wall of Knowledge,” the matrix of screens in the background that show patient and OR data, high-resolution video of surgical and laboratory images, and two real-time monitors for viewing radiographs.
“Dashboard” data monitoring
One component of the “Wall of Knowledge” is the OR-Dashboard (LiveData, Inc, Cambridge, MA) that captures data from multiple information systems, physiological monitors, and medical devices and displays it to the OR team.
PHOTOGRAPH BY RICHARD DEWITT, COURTESY MEMORIAL SLOAN-KETTERING CANCER CENTER, COURTESY LIVEDATA, INCThe goal is to develop safer systems, evaluate technology, and accumulate evidence to prove these technological innovations are effective. This also involves developing new processes for information management and patient flow.
Will Gyns share their OR?
SATAVA: I think of two kinds of OR of the future: The near-term, in the next 20 years or so, will concentrate an information-based system, such as imaging, robots, computers, and just-in-time inventory.
Shared, yet specialty-specific OR
We will continue to have multiple ORs in the near future because we will still need specialization. Neurosurgeons, gynecologists, and pediatric surgeons will still find it difficult to share the same OR—no matter how flexible it is. What these multi-specialty ORs will have in common is the way they’ll leverage information technologies.
To the cell level and beyond
The second kind of OR of the future is longer term and harder to describe. Here, biotechnology and energy-directed systems will replace mechanical and, to an extent, information-based systems. For example, in 30–50 years we’ll be using lasers for intracellular operations. Rather than physicians injecting various drugs or immunochemistry, they will actually use lasers and optical tweezers and manipulate the various organs—the mitochondria, operate on the DNA directly, and change cell biology rather than remove organs.
Will your office be your OR?
SATAVA: A capital-intensive facility such as a hospital or dedicated outpatient surgery center for complicated procedures will always have its place, although we’ve seen more minimally invasive surgery move out of the hospital. Beyond minimally invasive procedures are noninvasive procedures. High-intensity focused ultrasound and terahertz energy are the types of technologies that can safely move out of an operating room.
And a CT is not an imaging device, but an information system with eyes. Robotic machines and imaging devices can be integrated into “information space” in ways that are elusive in real space. “Information space” sees no difference between a process and an object.
Our product is our patient
Health care is the only industry that does not have an information representation of its product. Our product is our patient. We cannot use the hardware and software that all other industries use for virtual prototyping and testing.
Health care does not understand systems integration. We’ve spent a century dissecting the human into 26 different National Institutes of Health that don’t talk to each other.
We can reintegrate the human at the workstation and surgeon, where supply chain management, just-in-time inventory, robotics, and imaging for surgical rehearsal can come together.
Pre-op, literally
The robot can capture a surgeon’s hand motions and play them back with 10–12 times the accuracy at 7–15 times the speed. In the long-term, the surgeon would get the image of the patient in the OR just before the operation, perform the motions of the operation, and edit out the mistakes until the procedure is perfect.
When the surgeon is finished, he or she sends the edited, perfected operation to the robot, which performs it accurately and with greater speed. Appendectomies and cholecystectomies would take 10 minutes; Whipple procedures 45 minutes.
Richard M. Satava, MD
Big hospitals believe in generic ORs. Do we have scientific proof of what is best?
SANDBERG: OR design is not a science. No peer-reviewed literature in OR architecture exists. Few if any studies have actually tested the effectiveness of a given OR design.
The OR is a gigantic medical device that encloses the patient and staff. It ought to be studied in a rigorous and, ideally, prospective way, although such studies would be very expensive.
SATAVA: Moving toward noninvasive surgery doesn’t mean that open and minimally invasive surgery are going away. However, I don’t see anything in the near term that will make computed tomography (CT), magnetic resonance imaging (MRI), and new terahertz technology small enough to share space in one room.
On the other hand, robotics are moving us toward an OR with no staff. Put the patient in, and the surgeon on the outside will operate robotically. We could see that in the next 4–5 years. Biosurgery may create a need for quarantine or isolation. We’ll still have these multiple ORs in the future.
PARK: Look at the last 15 years and how long it has taken certain minimally invasive techniques to become mainstream. Only now are we getting the OR suites to accommodate them.
It’s a challenge that such little scholarly study has been undertaken. We need to push industry and hospital administrators to bring modularity to the ORs now on the drawing board. It’s ambitious, but it’s a way to start.
What outcomes matter the most?
SANDBERG: The commonly discussed outcome variables are procedure time, and hospital cost and revenue—but they’re not necessarily the right metrics.
What we’re looking for is a metric that captures the patient benefits and risks. Then we need to determine if the surgeons, the nurses, the anesthesiologists, the technologists, and the informationists can use this near-term OR of the future effectively for the patient’s benefit.
PARK: Designing studies is one of the real challenges in trying to generate data in this field. These studies tend to start out looking at global principles but end up fixating on operational issues—for example, how to get a pair of sharp scissors to an OR on a regular basis.
This is going to bring new metrics to the operating room—concepts such as process mapping, and workflow and workspace assessments.
Robotics gives us the chance to rehearse an operation. How practical are rehearsals?
No warm-ups for surgeons
SATAVA: I don’t know of any other profession that immediately starts to work without warming up or practicing.
I’ve never seen a baseball player run from the dugout to the batter’s box.
I’ve never seen a symphony orchestra run right out and start playing.
Why don’t we do a little rehearsing and practice the hardest parts before we actually start the incision?
Still, this won’t become cost-effective in the near term.
“Cognitive” rehearsals
PARK: You can rehearse selectively, based on the difficulty or complexity. We rehearse complex anti-reflux procedures and donor nephrectomies. Software models the patient’s data, and I will do a “fly-through” the afternoon before a laparoscopic donor nephrectomy.
Rehearsal at this stage has more to do with the cognitive processes than technical. So whether I need to practice taking that fat off the renal hilum is less of an issue than the position of lumbar veins or the relation of the renal vein to the aorta.
I feel immensely better prepared for the surgery when I’ve done that fly-through. I’m hard pressed to give you a good metric, to show the science to support it, but I believe there’s a role for it.
SANDBERG: This gets back to the question of metrics. Much of what we’re seeing as we look at ORs of the future actually improves the work experience for the surgeon, anesthesiologist, and nurses.
You can’t put a dollar value on that unless you’re talking about the cost of recruiting and training staff, but it does seem to improve outcomes for the people who work in the OR—and that must translate to patient outcomes. It’s difficult to justify to an administrator, but on a moral level it seems like the right thing to do.
The ideal would be a robotic anesthetist who would not be in the coffee lounge when you want to turn over your case.
“Robo-doc” anesthetist
SANDBERG: Making a business case for a robot for anesthesia is even harder. Functions such as vascular access and airway control are easy to an expert, but I don’t know yet of anyone who even attempted to make an IV-starting robot.
SATAVA: We have one.
SANDBERG: I’ve seen your prototypes. I don’t think you can program your “Robo-doc” to anesthetize the patient when you want, but the maintenance phase is one area in anesthesia ripe for automation.
Anesthesiology is actually in the driver’s seat for harvesting, controlling, and integrating information in the OR. Our project integrates data that anesthesiologists traditionally managed with that from surgical instruments and hospital information systems to create a total patient picture. That includes interventions and perturbations caused by surgery. Once that’s in place, you could imagine actually driving the anesthetic using closed-loop control.
SATAVA: Anesthesia is probably going to evolve more than surgery thanks to safer anesthetics and new nanotechnology. The new anesthetic autoregulators will make it almost impossible to overdose or under-dose a patient.
Are “smart” instruments equal to our own fingertips?
PARK: Today we can make a standard (open surgery) incision into which we insert one or both hands and have more than 20° of movement with the benefit of an innervated end effecter—our fingertips.
The OR of the future will put us in a situation where we’re disconnected in the tactile sense from the target anatomy and limit us to 4°–8° of movement. The stimulus is to get those degrees of movement back to compensate for the tactile feedback we’ve lost.
Hand-assisted laparoscopy is a lowtech way for getting around that loss of movement. It’s nothing other than a transition step, but it’s a clever solution.
How did you discover “parallel processing” to save costs and time?
SANDBERG: We tried to deconstruct the perioperative process immediately upstream and downstream of the OR itself, then we tested the time savings and cost effectiveness of the new process.1
ORs in America tend to do things sequentially via serial-processing work-flow: nurses and technologists set up the OR, the anesthesiologist brings in the patient and induces anesthetic, the surgery happens, the patient emerges from anesthesia, the anesthesiologist takes the patient to recovery.
We discovered that in any of these linear processes a team will be waiting for another team member to finish a task. That presented an opportunity to increase the effectiveness of the OR by finding a way for those team members to work in parallel rather than in sequence.
At Massachusetts General, we reduced the nonoperative time from when the surgeon steps back from the patient until the surgeon steps up to prep the next patient, from roughly 70 to 40 minutes by implementing a couple of parallel processing interventions. Other reports have verified this approach.2,3
In the MGH project, however, the interface between that particular OR and the hospital became problematic when the OR sent patients to the floor faster than the hospital could accept them.
What happened when the conveyor belt speeded up?
This gets us to the notion of perioperative systems design, which is basically a fantastic accident at most hospitals. In our OR of the Future project at MGH, we isolated part of the perioperative process, optimized it, and in so doing we broke the recovery room and upstream admission process. It was like transplanting an elephant heart into a mouse.
What is “plug-and-play”?
SATAVA: Plug-and-play would standardize interfacing between similar components that are interchangeable. Let’s say we have 6 different EKG machines, each with a different method for plugging in the leads. Our concept of plug-and-play goes from software that talks between devices to interchangeable tubing and electrical connections to the devices themselves. This standard is necessary to achieve even the most rudimentary information-based OR of the future.
Lack of plug-and-play connectivity has made it difficult even to get a patient’s allergy information from one database to another. At our institution, a couple software engineers took about 3 months to accomplish that. If this is what it takes to integrate 1 piece of information at 1 institution, we don’t have a chance.
Where do things stand with radiofrequency identification tagging?
PARK: Two types of RFID tags exist: A passive tag is a simple tag that when interrogated by a local node or cell just says it’s there. An active tag imparts a lot more information.
SANDBERG: An RFID tag would contain a patient’s critical medical data, but this vision has many problems at the moment. A tag with sufficient data storage is very expensive.
Security is another problem. The information is transmitted wirelessly and the encryption consumes tag memory. Passive RFID tags, which don’t require a battery and cost less to produce, simply can’t store enough information to be useful as a repository of medical data.
So we’ve discovered applications for RFID beyond the mobile patient record on the tag wristband. RFID can, at least in theory, be used for inventory management. Again, the problems with its costs and the need to scan the items limits its usefulness. Hospitals can use active RFID tags now for tracking high-value assets—not only expensive medical equipment but also personnel and patients.
PARK: We’ve been evaluating many different location RFID technologies in the operating room. We’ve found that the resolution of these technologies is miles from the manufacturers’ claims.
SATAVA: The trade-off for security is the inverse relationship between the level of security and the amount of computing power it demands, along with the amount of physical space available on the device.
Maybe in two years the computing power will increase and device size decrease, so we can get more on a smaller object, and its costs will decrease.
SANDBERG: Another problem with passive RFID is a high out-of-box failure rate. The antennae break off in manufacturing and shipping.
Besides cost, spatial resolution is another problem with active tags. On the other hand, passive RFID tags can have sub-centimeter resolution because the reader has to be so close to read the tag.
However, scanning the tag is another problem. Most of us in our workflows don’t have time to grab an RFID reader. Passive RFID reader technology is far from ideal for a busy OR.
Ideally, they should require no effort: objects brought into the OR would register on an as-yet-uninvented meter and localize in the room, ideally at 1 cm resolution or better.
What devices will be the stars of the OR of the Future?
LED Technology
SATAVA: With LED—light-emitting diode—technology and the small cameras now in cell phones, we have the opportunity to get rid of all the lights in the operating room.
The University of Barcelona has accomplished this.4 A sea of 100 to 150 cameras is placed around the room. You don’t have to move the cameras or lights. This clears up all the booms that are hanging down of these enormously inefficient lights that we have today.
This technology can leverage information systems that talk to objects and track instruments.
Wireless, miniaturized robots
PARK: Miniaturized robots, designed to be wireless in the near future, can actually rove the peritoneal cavity equipped with an end effecter or mobile camera. Dropped in through a 5- or 10-mm port, these devices can get to the target anatomy. Mechanical miniaturization is another way of getting around the loss of degrees of movement.
Better visualization with HD video
The minimally invasive revolution has moved us from having direct binocular visual contact with the target anatomy to working in a 3-dimensional space off a 2-dimensional image.
The next step is to take the vast amount of data we’re capturing, especially with HD video, from the operative field and use it to improve surgical visualization and ultimately outcomes.
This may involve real-time modeling and altering the visual perspective of the operative field as it is presented to the surgeon. We’re looking at new ways of making the data more intuitive.
Beyond the visible spectrum
SATAVA: There’s another dimension: Why are we only using cameras that see in the visible spectrum? Why aren’t we using infrared and ultraviolet cameras as other industries do?
We may not need the sense of touch because an infrared camera can show us all the blood vessels by temperature change. Health care hasn’t even looked at off-the-shelf technologies that other industries have used for 25 years.
PARK: Narrow-band imaging and confocal microscopy are now available, but we haven’t even started to look at how we could apply them intra-abdominally.
Will biotechnology bring down the curtain on surgeons?
SATAVA: We haven’t talked about the extraordinary revolution in biotechnology and how it’s either going to change the way a surgeon works or puts the surgeon out of business.
We may not have to do surgery if we can manipulate tissue on a molecular level. That’s 20–25 years out. It’s going to take that long for nanotechnology to develop usable products for health care.
The human element
RATTNER: We didn’t dwell on the human factor. The functioning of a highly skilled team and the interaction among team members is fertile ground for further research. Greater attention paid to team training and simulation crisis management will pay off in patient safety.
At the end of the day, the priority is that if we’re going to operate faster and more efficiently with more complex procedures, we have to get to Six Sigma or better safety levels.
Disclosures
Dr Park disclosed an affiliation with Stryker Endoscopy. Dr Sandberg disclosed affiliations with LiveData, Inc, Cambridge, MA; and Radianse, Inc, Lawrence, MA. Dr Satava disclosed an affiliation with Medical Education Technologies, Inc, Sarasota, FL. Dr Rattner had no affiliations to disclose.
1. Sandberg WS, Daily B, Egan M, et al. Deliberate perioperative systems design improves operating room throughput. Anesthesiology. 2005;103:406-418.
2. Hanss R, Buttgereit B, Tonner PH, et al. Overlapping induction of anesthesia: an analysis of benefits and costs. Anesthesiology. 2005;103:391-400.
3. Torkki PM, Marjamaa RA, Torkki MI, Kallio PE, Kirvela OA. Use of anesthesia induction rooms can increase the number of urgent orthopedic cases completed within 7 hours. Anesthesiology. 2005;103:401-405.
4. LaPorte EN. Array of ceiling mounted LED lights for the OR of the Future. Paper presented at: 12th European Association of Endoscopic Surgeons (EAES) Congress; June 9-12, 2004, Barcelona, Spain.
What will the operating room of the future look like? Will it be a specialty-specific facility or a generic OR? Our Symposium panelists, each a primary investigator in an “OR of the Future” project at his own institution, share their ideas of what the future holds, from getting clutter off the floor and onto the ceiling, to integrating patient information, imaging, and robotic systems.
Panelists also share their visions of what the OR may look like in 25 years and what obstacles need to be overcome to make the futuristic vision a reality. Robotics, smart displays, information management and integration, and image-guided surgery may become as common as the stapler and the scalpel.
Dr. Rattner
The making of the “OR of the Future”
PARK: It’s been said that the operating room of the future means that we take the clutter off the floor and put it on the ceiling, but we need to have a much broader view.
“OR of the Future” embodies a vision of improved patient safety and outcomes—from evaluating and assimilating existing technologies, to identifying technologies that need to be developed or brought in, to integrating the technologies that will get us there.
SANDBERG: The “OR of the Future” is also about therapeutic effectiveness for our patients and organizational effectiveness for the hospital.
The OR of the future is a concept through which a big organization such as an academic hospital can foster innovative projects. It can designate a place within its own organization that’s politically, financially, and physically separate from the main workflow and objectives, where the hospital can test processes and technologies.
“Wall of Knowledge”
A matrix of real-time screens
This operating room at Memorial Sloan-Kettering Cancer Center is one of 21 that employ the “Wall of Knowledge,” the matrix of screens in the background that show patient and OR data, high-resolution video of surgical and laboratory images, and two real-time monitors for viewing radiographs.
“Dashboard” data monitoring
One component of the “Wall of Knowledge” is the OR-Dashboard (LiveData, Inc, Cambridge, MA) that captures data from multiple information systems, physiological monitors, and medical devices and displays it to the OR team.
PHOTOGRAPH BY RICHARD DEWITT, COURTESY MEMORIAL SLOAN-KETTERING CANCER CENTER, COURTESY LIVEDATA, INCThe goal is to develop safer systems, evaluate technology, and accumulate evidence to prove these technological innovations are effective. This also involves developing new processes for information management and patient flow.
Will Gyns share their OR?
SATAVA: I think of two kinds of OR of the future: The near-term, in the next 20 years or so, will concentrate an information-based system, such as imaging, robots, computers, and just-in-time inventory.
Shared, yet specialty-specific OR
We will continue to have multiple ORs in the near future because we will still need specialization. Neurosurgeons, gynecologists, and pediatric surgeons will still find it difficult to share the same OR—no matter how flexible it is. What these multi-specialty ORs will have in common is the way they’ll leverage information technologies.
To the cell level and beyond
The second kind of OR of the future is longer term and harder to describe. Here, biotechnology and energy-directed systems will replace mechanical and, to an extent, information-based systems. For example, in 30–50 years we’ll be using lasers for intracellular operations. Rather than physicians injecting various drugs or immunochemistry, they will actually use lasers and optical tweezers and manipulate the various organs—the mitochondria, operate on the DNA directly, and change cell biology rather than remove organs.
Will your office be your OR?
SATAVA: A capital-intensive facility such as a hospital or dedicated outpatient surgery center for complicated procedures will always have its place, although we’ve seen more minimally invasive surgery move out of the hospital. Beyond minimally invasive procedures are noninvasive procedures. High-intensity focused ultrasound and terahertz energy are the types of technologies that can safely move out of an operating room.
And a CT is not an imaging device, but an information system with eyes. Robotic machines and imaging devices can be integrated into “information space” in ways that are elusive in real space. “Information space” sees no difference between a process and an object.
Our product is our patient
Health care is the only industry that does not have an information representation of its product. Our product is our patient. We cannot use the hardware and software that all other industries use for virtual prototyping and testing.
Health care does not understand systems integration. We’ve spent a century dissecting the human into 26 different National Institutes of Health that don’t talk to each other.
We can reintegrate the human at the workstation and surgeon, where supply chain management, just-in-time inventory, robotics, and imaging for surgical rehearsal can come together.
Pre-op, literally
The robot can capture a surgeon’s hand motions and play them back with 10–12 times the accuracy at 7–15 times the speed. In the long-term, the surgeon would get the image of the patient in the OR just before the operation, perform the motions of the operation, and edit out the mistakes until the procedure is perfect.
When the surgeon is finished, he or she sends the edited, perfected operation to the robot, which performs it accurately and with greater speed. Appendectomies and cholecystectomies would take 10 minutes; Whipple procedures 45 minutes.
Richard M. Satava, MD
Big hospitals believe in generic ORs. Do we have scientific proof of what is best?
SANDBERG: OR design is not a science. No peer-reviewed literature in OR architecture exists. Few if any studies have actually tested the effectiveness of a given OR design.
The OR is a gigantic medical device that encloses the patient and staff. It ought to be studied in a rigorous and, ideally, prospective way, although such studies would be very expensive.
SATAVA: Moving toward noninvasive surgery doesn’t mean that open and minimally invasive surgery are going away. However, I don’t see anything in the near term that will make computed tomography (CT), magnetic resonance imaging (MRI), and new terahertz technology small enough to share space in one room.
On the other hand, robotics are moving us toward an OR with no staff. Put the patient in, and the surgeon on the outside will operate robotically. We could see that in the next 4–5 years. Biosurgery may create a need for quarantine or isolation. We’ll still have these multiple ORs in the future.
PARK: Look at the last 15 years and how long it has taken certain minimally invasive techniques to become mainstream. Only now are we getting the OR suites to accommodate them.
It’s a challenge that such little scholarly study has been undertaken. We need to push industry and hospital administrators to bring modularity to the ORs now on the drawing board. It’s ambitious, but it’s a way to start.
What outcomes matter the most?
SANDBERG: The commonly discussed outcome variables are procedure time, and hospital cost and revenue—but they’re not necessarily the right metrics.
What we’re looking for is a metric that captures the patient benefits and risks. Then we need to determine if the surgeons, the nurses, the anesthesiologists, the technologists, and the informationists can use this near-term OR of the future effectively for the patient’s benefit.
PARK: Designing studies is one of the real challenges in trying to generate data in this field. These studies tend to start out looking at global principles but end up fixating on operational issues—for example, how to get a pair of sharp scissors to an OR on a regular basis.
This is going to bring new metrics to the operating room—concepts such as process mapping, and workflow and workspace assessments.
Robotics gives us the chance to rehearse an operation. How practical are rehearsals?
No warm-ups for surgeons
SATAVA: I don’t know of any other profession that immediately starts to work without warming up or practicing.
I’ve never seen a baseball player run from the dugout to the batter’s box.
I’ve never seen a symphony orchestra run right out and start playing.
Why don’t we do a little rehearsing and practice the hardest parts before we actually start the incision?
Still, this won’t become cost-effective in the near term.
“Cognitive” rehearsals
PARK: You can rehearse selectively, based on the difficulty or complexity. We rehearse complex anti-reflux procedures and donor nephrectomies. Software models the patient’s data, and I will do a “fly-through” the afternoon before a laparoscopic donor nephrectomy.
Rehearsal at this stage has more to do with the cognitive processes than technical. So whether I need to practice taking that fat off the renal hilum is less of an issue than the position of lumbar veins or the relation of the renal vein to the aorta.
I feel immensely better prepared for the surgery when I’ve done that fly-through. I’m hard pressed to give you a good metric, to show the science to support it, but I believe there’s a role for it.
SANDBERG: This gets back to the question of metrics. Much of what we’re seeing as we look at ORs of the future actually improves the work experience for the surgeon, anesthesiologist, and nurses.
You can’t put a dollar value on that unless you’re talking about the cost of recruiting and training staff, but it does seem to improve outcomes for the people who work in the OR—and that must translate to patient outcomes. It’s difficult to justify to an administrator, but on a moral level it seems like the right thing to do.
The ideal would be a robotic anesthetist who would not be in the coffee lounge when you want to turn over your case.
“Robo-doc” anesthetist
SANDBERG: Making a business case for a robot for anesthesia is even harder. Functions such as vascular access and airway control are easy to an expert, but I don’t know yet of anyone who even attempted to make an IV-starting robot.
SATAVA: We have one.
SANDBERG: I’ve seen your prototypes. I don’t think you can program your “Robo-doc” to anesthetize the patient when you want, but the maintenance phase is one area in anesthesia ripe for automation.
Anesthesiology is actually in the driver’s seat for harvesting, controlling, and integrating information in the OR. Our project integrates data that anesthesiologists traditionally managed with that from surgical instruments and hospital information systems to create a total patient picture. That includes interventions and perturbations caused by surgery. Once that’s in place, you could imagine actually driving the anesthetic using closed-loop control.
SATAVA: Anesthesia is probably going to evolve more than surgery thanks to safer anesthetics and new nanotechnology. The new anesthetic autoregulators will make it almost impossible to overdose or under-dose a patient.
Are “smart” instruments equal to our own fingertips?
PARK: Today we can make a standard (open surgery) incision into which we insert one or both hands and have more than 20° of movement with the benefit of an innervated end effecter—our fingertips.
The OR of the future will put us in a situation where we’re disconnected in the tactile sense from the target anatomy and limit us to 4°–8° of movement. The stimulus is to get those degrees of movement back to compensate for the tactile feedback we’ve lost.
Hand-assisted laparoscopy is a lowtech way for getting around that loss of movement. It’s nothing other than a transition step, but it’s a clever solution.
How did you discover “parallel processing” to save costs and time?
SANDBERG: We tried to deconstruct the perioperative process immediately upstream and downstream of the OR itself, then we tested the time savings and cost effectiveness of the new process.1
ORs in America tend to do things sequentially via serial-processing work-flow: nurses and technologists set up the OR, the anesthesiologist brings in the patient and induces anesthetic, the surgery happens, the patient emerges from anesthesia, the anesthesiologist takes the patient to recovery.
We discovered that in any of these linear processes a team will be waiting for another team member to finish a task. That presented an opportunity to increase the effectiveness of the OR by finding a way for those team members to work in parallel rather than in sequence.
At Massachusetts General, we reduced the nonoperative time from when the surgeon steps back from the patient until the surgeon steps up to prep the next patient, from roughly 70 to 40 minutes by implementing a couple of parallel processing interventions. Other reports have verified this approach.2,3
In the MGH project, however, the interface between that particular OR and the hospital became problematic when the OR sent patients to the floor faster than the hospital could accept them.
What happened when the conveyor belt speeded up?
This gets us to the notion of perioperative systems design, which is basically a fantastic accident at most hospitals. In our OR of the Future project at MGH, we isolated part of the perioperative process, optimized it, and in so doing we broke the recovery room and upstream admission process. It was like transplanting an elephant heart into a mouse.
What is “plug-and-play”?
SATAVA: Plug-and-play would standardize interfacing between similar components that are interchangeable. Let’s say we have 6 different EKG machines, each with a different method for plugging in the leads. Our concept of plug-and-play goes from software that talks between devices to interchangeable tubing and electrical connections to the devices themselves. This standard is necessary to achieve even the most rudimentary information-based OR of the future.
Lack of plug-and-play connectivity has made it difficult even to get a patient’s allergy information from one database to another. At our institution, a couple software engineers took about 3 months to accomplish that. If this is what it takes to integrate 1 piece of information at 1 institution, we don’t have a chance.
Where do things stand with radiofrequency identification tagging?
PARK: Two types of RFID tags exist: A passive tag is a simple tag that when interrogated by a local node or cell just says it’s there. An active tag imparts a lot more information.
SANDBERG: An RFID tag would contain a patient’s critical medical data, but this vision has many problems at the moment. A tag with sufficient data storage is very expensive.
Security is another problem. The information is transmitted wirelessly and the encryption consumes tag memory. Passive RFID tags, which don’t require a battery and cost less to produce, simply can’t store enough information to be useful as a repository of medical data.
So we’ve discovered applications for RFID beyond the mobile patient record on the tag wristband. RFID can, at least in theory, be used for inventory management. Again, the problems with its costs and the need to scan the items limits its usefulness. Hospitals can use active RFID tags now for tracking high-value assets—not only expensive medical equipment but also personnel and patients.
PARK: We’ve been evaluating many different location RFID technologies in the operating room. We’ve found that the resolution of these technologies is miles from the manufacturers’ claims.
SATAVA: The trade-off for security is the inverse relationship between the level of security and the amount of computing power it demands, along with the amount of physical space available on the device.
Maybe in two years the computing power will increase and device size decrease, so we can get more on a smaller object, and its costs will decrease.
SANDBERG: Another problem with passive RFID is a high out-of-box failure rate. The antennae break off in manufacturing and shipping.
Besides cost, spatial resolution is another problem with active tags. On the other hand, passive RFID tags can have sub-centimeter resolution because the reader has to be so close to read the tag.
However, scanning the tag is another problem. Most of us in our workflows don’t have time to grab an RFID reader. Passive RFID reader technology is far from ideal for a busy OR.
Ideally, they should require no effort: objects brought into the OR would register on an as-yet-uninvented meter and localize in the room, ideally at 1 cm resolution or better.
What devices will be the stars of the OR of the Future?
LED Technology
SATAVA: With LED—light-emitting diode—technology and the small cameras now in cell phones, we have the opportunity to get rid of all the lights in the operating room.
The University of Barcelona has accomplished this.4 A sea of 100 to 150 cameras is placed around the room. You don’t have to move the cameras or lights. This clears up all the booms that are hanging down of these enormously inefficient lights that we have today.
This technology can leverage information systems that talk to objects and track instruments.
Wireless, miniaturized robots
PARK: Miniaturized robots, designed to be wireless in the near future, can actually rove the peritoneal cavity equipped with an end effecter or mobile camera. Dropped in through a 5- or 10-mm port, these devices can get to the target anatomy. Mechanical miniaturization is another way of getting around the loss of degrees of movement.
Better visualization with HD video
The minimally invasive revolution has moved us from having direct binocular visual contact with the target anatomy to working in a 3-dimensional space off a 2-dimensional image.
The next step is to take the vast amount of data we’re capturing, especially with HD video, from the operative field and use it to improve surgical visualization and ultimately outcomes.
This may involve real-time modeling and altering the visual perspective of the operative field as it is presented to the surgeon. We’re looking at new ways of making the data more intuitive.
Beyond the visible spectrum
SATAVA: There’s another dimension: Why are we only using cameras that see in the visible spectrum? Why aren’t we using infrared and ultraviolet cameras as other industries do?
We may not need the sense of touch because an infrared camera can show us all the blood vessels by temperature change. Health care hasn’t even looked at off-the-shelf technologies that other industries have used for 25 years.
PARK: Narrow-band imaging and confocal microscopy are now available, but we haven’t even started to look at how we could apply them intra-abdominally.
Will biotechnology bring down the curtain on surgeons?
SATAVA: We haven’t talked about the extraordinary revolution in biotechnology and how it’s either going to change the way a surgeon works or puts the surgeon out of business.
We may not have to do surgery if we can manipulate tissue on a molecular level. That’s 20–25 years out. It’s going to take that long for nanotechnology to develop usable products for health care.
The human element
RATTNER: We didn’t dwell on the human factor. The functioning of a highly skilled team and the interaction among team members is fertile ground for further research. Greater attention paid to team training and simulation crisis management will pay off in patient safety.
At the end of the day, the priority is that if we’re going to operate faster and more efficiently with more complex procedures, we have to get to Six Sigma or better safety levels.
Disclosures
Dr Park disclosed an affiliation with Stryker Endoscopy. Dr Sandberg disclosed affiliations with LiveData, Inc, Cambridge, MA; and Radianse, Inc, Lawrence, MA. Dr Satava disclosed an affiliation with Medical Education Technologies, Inc, Sarasota, FL. Dr Rattner had no affiliations to disclose.
What will the operating room of the future look like? Will it be a specialty-specific facility or a generic OR? Our Symposium panelists, each a primary investigator in an “OR of the Future” project at his own institution, share their ideas of what the future holds, from getting clutter off the floor and onto the ceiling, to integrating patient information, imaging, and robotic systems.
Panelists also share their visions of what the OR may look like in 25 years and what obstacles need to be overcome to make the futuristic vision a reality. Robotics, smart displays, information management and integration, and image-guided surgery may become as common as the stapler and the scalpel.
Dr. Rattner
The making of the “OR of the Future”
PARK: It’s been said that the operating room of the future means that we take the clutter off the floor and put it on the ceiling, but we need to have a much broader view.
“OR of the Future” embodies a vision of improved patient safety and outcomes—from evaluating and assimilating existing technologies, to identifying technologies that need to be developed or brought in, to integrating the technologies that will get us there.
SANDBERG: The “OR of the Future” is also about therapeutic effectiveness for our patients and organizational effectiveness for the hospital.
The OR of the future is a concept through which a big organization such as an academic hospital can foster innovative projects. It can designate a place within its own organization that’s politically, financially, and physically separate from the main workflow and objectives, where the hospital can test processes and technologies.
“Wall of Knowledge”
A matrix of real-time screens
This operating room at Memorial Sloan-Kettering Cancer Center is one of 21 that employ the “Wall of Knowledge,” the matrix of screens in the background that show patient and OR data, high-resolution video of surgical and laboratory images, and two real-time monitors for viewing radiographs.
“Dashboard” data monitoring
One component of the “Wall of Knowledge” is the OR-Dashboard (LiveData, Inc, Cambridge, MA) that captures data from multiple information systems, physiological monitors, and medical devices and displays it to the OR team.
PHOTOGRAPH BY RICHARD DEWITT, COURTESY MEMORIAL SLOAN-KETTERING CANCER CENTER, COURTESY LIVEDATA, INCThe goal is to develop safer systems, evaluate technology, and accumulate evidence to prove these technological innovations are effective. This also involves developing new processes for information management and patient flow.
Will Gyns share their OR?
SATAVA: I think of two kinds of OR of the future: The near-term, in the next 20 years or so, will concentrate an information-based system, such as imaging, robots, computers, and just-in-time inventory.
Shared, yet specialty-specific OR
We will continue to have multiple ORs in the near future because we will still need specialization. Neurosurgeons, gynecologists, and pediatric surgeons will still find it difficult to share the same OR—no matter how flexible it is. What these multi-specialty ORs will have in common is the way they’ll leverage information technologies.
To the cell level and beyond
The second kind of OR of the future is longer term and harder to describe. Here, biotechnology and energy-directed systems will replace mechanical and, to an extent, information-based systems. For example, in 30–50 years we’ll be using lasers for intracellular operations. Rather than physicians injecting various drugs or immunochemistry, they will actually use lasers and optical tweezers and manipulate the various organs—the mitochondria, operate on the DNA directly, and change cell biology rather than remove organs.
Will your office be your OR?
SATAVA: A capital-intensive facility such as a hospital or dedicated outpatient surgery center for complicated procedures will always have its place, although we’ve seen more minimally invasive surgery move out of the hospital. Beyond minimally invasive procedures are noninvasive procedures. High-intensity focused ultrasound and terahertz energy are the types of technologies that can safely move out of an operating room.
And a CT is not an imaging device, but an information system with eyes. Robotic machines and imaging devices can be integrated into “information space” in ways that are elusive in real space. “Information space” sees no difference between a process and an object.
Our product is our patient
Health care is the only industry that does not have an information representation of its product. Our product is our patient. We cannot use the hardware and software that all other industries use for virtual prototyping and testing.
Health care does not understand systems integration. We’ve spent a century dissecting the human into 26 different National Institutes of Health that don’t talk to each other.
We can reintegrate the human at the workstation and surgeon, where supply chain management, just-in-time inventory, robotics, and imaging for surgical rehearsal can come together.
Pre-op, literally
The robot can capture a surgeon’s hand motions and play them back with 10–12 times the accuracy at 7–15 times the speed. In the long-term, the surgeon would get the image of the patient in the OR just before the operation, perform the motions of the operation, and edit out the mistakes until the procedure is perfect.
When the surgeon is finished, he or she sends the edited, perfected operation to the robot, which performs it accurately and with greater speed. Appendectomies and cholecystectomies would take 10 minutes; Whipple procedures 45 minutes.
Richard M. Satava, MD
Big hospitals believe in generic ORs. Do we have scientific proof of what is best?
SANDBERG: OR design is not a science. No peer-reviewed literature in OR architecture exists. Few if any studies have actually tested the effectiveness of a given OR design.
The OR is a gigantic medical device that encloses the patient and staff. It ought to be studied in a rigorous and, ideally, prospective way, although such studies would be very expensive.
SATAVA: Moving toward noninvasive surgery doesn’t mean that open and minimally invasive surgery are going away. However, I don’t see anything in the near term that will make computed tomography (CT), magnetic resonance imaging (MRI), and new terahertz technology small enough to share space in one room.
On the other hand, robotics are moving us toward an OR with no staff. Put the patient in, and the surgeon on the outside will operate robotically. We could see that in the next 4–5 years. Biosurgery may create a need for quarantine or isolation. We’ll still have these multiple ORs in the future.
PARK: Look at the last 15 years and how long it has taken certain minimally invasive techniques to become mainstream. Only now are we getting the OR suites to accommodate them.
It’s a challenge that such little scholarly study has been undertaken. We need to push industry and hospital administrators to bring modularity to the ORs now on the drawing board. It’s ambitious, but it’s a way to start.
What outcomes matter the most?
SANDBERG: The commonly discussed outcome variables are procedure time, and hospital cost and revenue—but they’re not necessarily the right metrics.
What we’re looking for is a metric that captures the patient benefits and risks. Then we need to determine if the surgeons, the nurses, the anesthesiologists, the technologists, and the informationists can use this near-term OR of the future effectively for the patient’s benefit.
PARK: Designing studies is one of the real challenges in trying to generate data in this field. These studies tend to start out looking at global principles but end up fixating on operational issues—for example, how to get a pair of sharp scissors to an OR on a regular basis.
This is going to bring new metrics to the operating room—concepts such as process mapping, and workflow and workspace assessments.
Robotics gives us the chance to rehearse an operation. How practical are rehearsals?
No warm-ups for surgeons
SATAVA: I don’t know of any other profession that immediately starts to work without warming up or practicing.
I’ve never seen a baseball player run from the dugout to the batter’s box.
I’ve never seen a symphony orchestra run right out and start playing.
Why don’t we do a little rehearsing and practice the hardest parts before we actually start the incision?
Still, this won’t become cost-effective in the near term.
“Cognitive” rehearsals
PARK: You can rehearse selectively, based on the difficulty or complexity. We rehearse complex anti-reflux procedures and donor nephrectomies. Software models the patient’s data, and I will do a “fly-through” the afternoon before a laparoscopic donor nephrectomy.
Rehearsal at this stage has more to do with the cognitive processes than technical. So whether I need to practice taking that fat off the renal hilum is less of an issue than the position of lumbar veins or the relation of the renal vein to the aorta.
I feel immensely better prepared for the surgery when I’ve done that fly-through. I’m hard pressed to give you a good metric, to show the science to support it, but I believe there’s a role for it.
SANDBERG: This gets back to the question of metrics. Much of what we’re seeing as we look at ORs of the future actually improves the work experience for the surgeon, anesthesiologist, and nurses.
You can’t put a dollar value on that unless you’re talking about the cost of recruiting and training staff, but it does seem to improve outcomes for the people who work in the OR—and that must translate to patient outcomes. It’s difficult to justify to an administrator, but on a moral level it seems like the right thing to do.
The ideal would be a robotic anesthetist who would not be in the coffee lounge when you want to turn over your case.
“Robo-doc” anesthetist
SANDBERG: Making a business case for a robot for anesthesia is even harder. Functions such as vascular access and airway control are easy to an expert, but I don’t know yet of anyone who even attempted to make an IV-starting robot.
SATAVA: We have one.
SANDBERG: I’ve seen your prototypes. I don’t think you can program your “Robo-doc” to anesthetize the patient when you want, but the maintenance phase is one area in anesthesia ripe for automation.
Anesthesiology is actually in the driver’s seat for harvesting, controlling, and integrating information in the OR. Our project integrates data that anesthesiologists traditionally managed with that from surgical instruments and hospital information systems to create a total patient picture. That includes interventions and perturbations caused by surgery. Once that’s in place, you could imagine actually driving the anesthetic using closed-loop control.
SATAVA: Anesthesia is probably going to evolve more than surgery thanks to safer anesthetics and new nanotechnology. The new anesthetic autoregulators will make it almost impossible to overdose or under-dose a patient.
Are “smart” instruments equal to our own fingertips?
PARK: Today we can make a standard (open surgery) incision into which we insert one or both hands and have more than 20° of movement with the benefit of an innervated end effecter—our fingertips.
The OR of the future will put us in a situation where we’re disconnected in the tactile sense from the target anatomy and limit us to 4°–8° of movement. The stimulus is to get those degrees of movement back to compensate for the tactile feedback we’ve lost.
Hand-assisted laparoscopy is a lowtech way for getting around that loss of movement. It’s nothing other than a transition step, but it’s a clever solution.
How did you discover “parallel processing” to save costs and time?
SANDBERG: We tried to deconstruct the perioperative process immediately upstream and downstream of the OR itself, then we tested the time savings and cost effectiveness of the new process.1
ORs in America tend to do things sequentially via serial-processing work-flow: nurses and technologists set up the OR, the anesthesiologist brings in the patient and induces anesthetic, the surgery happens, the patient emerges from anesthesia, the anesthesiologist takes the patient to recovery.
We discovered that in any of these linear processes a team will be waiting for another team member to finish a task. That presented an opportunity to increase the effectiveness of the OR by finding a way for those team members to work in parallel rather than in sequence.
At Massachusetts General, we reduced the nonoperative time from when the surgeon steps back from the patient until the surgeon steps up to prep the next patient, from roughly 70 to 40 minutes by implementing a couple of parallel processing interventions. Other reports have verified this approach.2,3
In the MGH project, however, the interface between that particular OR and the hospital became problematic when the OR sent patients to the floor faster than the hospital could accept them.
What happened when the conveyor belt speeded up?
This gets us to the notion of perioperative systems design, which is basically a fantastic accident at most hospitals. In our OR of the Future project at MGH, we isolated part of the perioperative process, optimized it, and in so doing we broke the recovery room and upstream admission process. It was like transplanting an elephant heart into a mouse.
What is “plug-and-play”?
SATAVA: Plug-and-play would standardize interfacing between similar components that are interchangeable. Let’s say we have 6 different EKG machines, each with a different method for plugging in the leads. Our concept of plug-and-play goes from software that talks between devices to interchangeable tubing and electrical connections to the devices themselves. This standard is necessary to achieve even the most rudimentary information-based OR of the future.
Lack of plug-and-play connectivity has made it difficult even to get a patient’s allergy information from one database to another. At our institution, a couple software engineers took about 3 months to accomplish that. If this is what it takes to integrate 1 piece of information at 1 institution, we don’t have a chance.
Where do things stand with radiofrequency identification tagging?
PARK: Two types of RFID tags exist: A passive tag is a simple tag that when interrogated by a local node or cell just says it’s there. An active tag imparts a lot more information.
SANDBERG: An RFID tag would contain a patient’s critical medical data, but this vision has many problems at the moment. A tag with sufficient data storage is very expensive.
Security is another problem. The information is transmitted wirelessly and the encryption consumes tag memory. Passive RFID tags, which don’t require a battery and cost less to produce, simply can’t store enough information to be useful as a repository of medical data.
So we’ve discovered applications for RFID beyond the mobile patient record on the tag wristband. RFID can, at least in theory, be used for inventory management. Again, the problems with its costs and the need to scan the items limits its usefulness. Hospitals can use active RFID tags now for tracking high-value assets—not only expensive medical equipment but also personnel and patients.
PARK: We’ve been evaluating many different location RFID technologies in the operating room. We’ve found that the resolution of these technologies is miles from the manufacturers’ claims.
SATAVA: The trade-off for security is the inverse relationship between the level of security and the amount of computing power it demands, along with the amount of physical space available on the device.
Maybe in two years the computing power will increase and device size decrease, so we can get more on a smaller object, and its costs will decrease.
SANDBERG: Another problem with passive RFID is a high out-of-box failure rate. The antennae break off in manufacturing and shipping.
Besides cost, spatial resolution is another problem with active tags. On the other hand, passive RFID tags can have sub-centimeter resolution because the reader has to be so close to read the tag.
However, scanning the tag is another problem. Most of us in our workflows don’t have time to grab an RFID reader. Passive RFID reader technology is far from ideal for a busy OR.
Ideally, they should require no effort: objects brought into the OR would register on an as-yet-uninvented meter and localize in the room, ideally at 1 cm resolution or better.
What devices will be the stars of the OR of the Future?
LED Technology
SATAVA: With LED—light-emitting diode—technology and the small cameras now in cell phones, we have the opportunity to get rid of all the lights in the operating room.
The University of Barcelona has accomplished this.4 A sea of 100 to 150 cameras is placed around the room. You don’t have to move the cameras or lights. This clears up all the booms that are hanging down of these enormously inefficient lights that we have today.
This technology can leverage information systems that talk to objects and track instruments.
Wireless, miniaturized robots
PARK: Miniaturized robots, designed to be wireless in the near future, can actually rove the peritoneal cavity equipped with an end effecter or mobile camera. Dropped in through a 5- or 10-mm port, these devices can get to the target anatomy. Mechanical miniaturization is another way of getting around the loss of degrees of movement.
Better visualization with HD video
The minimally invasive revolution has moved us from having direct binocular visual contact with the target anatomy to working in a 3-dimensional space off a 2-dimensional image.
The next step is to take the vast amount of data we’re capturing, especially with HD video, from the operative field and use it to improve surgical visualization and ultimately outcomes.
This may involve real-time modeling and altering the visual perspective of the operative field as it is presented to the surgeon. We’re looking at new ways of making the data more intuitive.
Beyond the visible spectrum
SATAVA: There’s another dimension: Why are we only using cameras that see in the visible spectrum? Why aren’t we using infrared and ultraviolet cameras as other industries do?
We may not need the sense of touch because an infrared camera can show us all the blood vessels by temperature change. Health care hasn’t even looked at off-the-shelf technologies that other industries have used for 25 years.
PARK: Narrow-band imaging and confocal microscopy are now available, but we haven’t even started to look at how we could apply them intra-abdominally.
Will biotechnology bring down the curtain on surgeons?
SATAVA: We haven’t talked about the extraordinary revolution in biotechnology and how it’s either going to change the way a surgeon works or puts the surgeon out of business.
We may not have to do surgery if we can manipulate tissue on a molecular level. That’s 20–25 years out. It’s going to take that long for nanotechnology to develop usable products for health care.
The human element
RATTNER: We didn’t dwell on the human factor. The functioning of a highly skilled team and the interaction among team members is fertile ground for further research. Greater attention paid to team training and simulation crisis management will pay off in patient safety.
At the end of the day, the priority is that if we’re going to operate faster and more efficiently with more complex procedures, we have to get to Six Sigma or better safety levels.
Disclosures
Dr Park disclosed an affiliation with Stryker Endoscopy. Dr Sandberg disclosed affiliations with LiveData, Inc, Cambridge, MA; and Radianse, Inc, Lawrence, MA. Dr Satava disclosed an affiliation with Medical Education Technologies, Inc, Sarasota, FL. Dr Rattner had no affiliations to disclose.
1. Sandberg WS, Daily B, Egan M, et al. Deliberate perioperative systems design improves operating room throughput. Anesthesiology. 2005;103:406-418.
2. Hanss R, Buttgereit B, Tonner PH, et al. Overlapping induction of anesthesia: an analysis of benefits and costs. Anesthesiology. 2005;103:391-400.
3. Torkki PM, Marjamaa RA, Torkki MI, Kallio PE, Kirvela OA. Use of anesthesia induction rooms can increase the number of urgent orthopedic cases completed within 7 hours. Anesthesiology. 2005;103:401-405.
4. LaPorte EN. Array of ceiling mounted LED lights for the OR of the Future. Paper presented at: 12th European Association of Endoscopic Surgeons (EAES) Congress; June 9-12, 2004, Barcelona, Spain.
1. Sandberg WS, Daily B, Egan M, et al. Deliberate perioperative systems design improves operating room throughput. Anesthesiology. 2005;103:406-418.
2. Hanss R, Buttgereit B, Tonner PH, et al. Overlapping induction of anesthesia: an analysis of benefits and costs. Anesthesiology. 2005;103:391-400.
3. Torkki PM, Marjamaa RA, Torkki MI, Kallio PE, Kirvela OA. Use of anesthesia induction rooms can increase the number of urgent orthopedic cases completed within 7 hours. Anesthesiology. 2005;103:401-405.
4. LaPorte EN. Array of ceiling mounted LED lights for the OR of the Future. Paper presented at: 12th European Association of Endoscopic Surgeons (EAES) Congress; June 9-12, 2004, Barcelona, Spain.
Outcomes, Costs, and Utilization of Pregnancy-Related Care
Predicting Dementia of the Alzheimer Type Using Cognistat
Everything you need to know about the contraceptive implant
On July 17, the US Food and Drug Administration (FDA) approved what may be the most effective hormonal contraceptive ever developed, a single-rod implant that goes by the trade name Implanon. The implant contains 68 mg of etonogestrel (ENG), the active metabolite of desogestrel, in a membrane of ethylene vinyl acetate. In clinical trials involving 20,648 cycles of exposure, only 6 pregnancies occurred, for a cumulative Pearl Index of 0.38 per 100 woman-years.1
This article reviews:
- the 2 contraceptive mechanisms
- indications and patient selection
- pharmacology, safety, adverse effects
- patient satisfaction and discontinuation rates
- insertion and removal
- key points of patient counseling
Unlike Norplant, a multi-rod implant which garnered a million American users before it was removed from the market, the single-rod implant is easy to insert and remove. Before you can order the implant, you must complete a manufacturer-sponsored training program.
Which patients are suitable candidates?
Because the subdermal implant contains only progestin, provides up to 3 years of protection, and requires no daily, weekly, or even monthly action on the part of the user, it is well-suited for:
- Women who wish to or need to avoid estrogen
- Teens who find adherence to a contraceptive regimen difficult
- Healthy adult women who desire long-term protection
- Women who are breastfeeding
Pros and cons
Advantages include:
- Cost. A study2 of 15 contraceptive methods found the implant cost-effective compared to short-acting methods, provided it was used long-term. As of press time, the manufacturer had not released the price.
- Short fertility-recovery time.
- No serious cardiovascular effects.3
Drawbacks. Progestin-only contraceptives also have disadvantages:
- Implants require a minor surgical procedure by trained clinicians for insertion and removal.
- Cost-effectiveness depends on duration of use; early discontinuation negates this benefit.2
- The implant does not protect against sexually transmitted infections—this is a disadvantage of all contraceptive methods except condoms and, perhaps, other barrier methods.
After Implanon is inserted just below the dermis 6 to 8 cm above the elbow crease on the inner aspect of the arm, it remains effective for up to 3 years. To remove it, make a 2-mm incision at the distal tip of the implant and push on the other end of the rod until it pops out.
The implant resides beneath the dermis but above the subcutaneous fat. It remains palpable but invisible, releasing about 60 μg of etonogestrel per day
Images: Rich Larocco
The Norplant experience
Research and development of progestin-only subdermal implants began more than 35 years ago, but early research involving very-low-dose implants found that they did not prevent ectopic pregnancies. This problem ended with Norplant, a 6-capsule implant using the potent progestin levonorgestrel (LNG).
Norplant was highly effective. Over 7 years of use, fewer than 1% of women became pregnant.4 Despite low pregnancy rates and few serious side effects, limitations in component supplies and negative media coverage on complications with removal led to its withdrawal in 2002, leaving no implant available in the US.5
The antiestrogenic effect
Long-acting, progestin-only contraceptives such as the new implant, the LNG-releasing intrauterine system (Mirena), and injectable methods (Depo-Provera) are safer than oral contraceptives (OCs) because they lack estrogen, which can provoke deep venous thrombosis.6,7
LNG, the gonane progestin used in Norplant, binds with high affinity to the progesterone, androgen, mineralocorticoid, and glucocorticoid receptors, but not to estrogen receptors. ENG, also known as 3-keto-desogestrel, demonstrates no estrogenic, anti-inflammatory, or mineralocorticoid activity, but has shown weak androgenic and anabolic activity, as well as strong antiestrogenic activity.
Unlike LNG, which binds mainly to sex hormone-binding globulin, ENG binds mainly to albumin, which is not affected by varying endogenous or exogenous estradiol levels. The safety of ENG has been demonstrated in studies of combined estrogen-progestin OCs and progestin-only OCs that use desogestrel as a component.
The progestin-only implant has 2 primary mechanisms:
- Inhibition of ovulation
- Restriction of sperm penetration of cervical mucus28
Ovulation is suppressed. LNG implants disrupt follicular growth and inhibit ovulation by exerting negative feedback on the hypothalamic–pituitary axis, causing a variety of changes, from anovulation to insufficient luteal function. A few women using LNG implants have quiescent ovaries, but most begin to ovulate as LNG blood concentrations gradually fall.29 The ENG implant suppresses ovulation by altering the hypothalamic–pituitary–ovarian axis and down-regulating the luteinizing hormone surge, which is required to support the production, growth, and maturation of ovarian follicles.11
Oocytes are not fertilized, even if follicles grow during use of the progestin implant. If the follicle ruptures, abnormalities of the ovulatory process prevent release of a viable egg.
Sperm cannot penetrate the cervical mucus. The antiestrogenic action of the progestin renders the cervical mucus viscous, scanty, and impenetrable by sperm.12
Contraceptive effects occur before fertilization
No signs of embryonic development have been found among implant users, indicating the implant lacks abortifacient properties.
Desogestrel in combination with ethinyl estradiol may slightly increase the attributable risk of deep venous thrombosis, but this response has not been shown without estrogen.
Design features
The single-rod design means little discomfort for patients at insertion or removal, an unobtrusive implant, and almost no scarring. Insertion and removal are predictably brief. In US and European trials, which began 10 years ago, average insertion time was 1 minute, and removal time was 3 minutes. In contrast, Norplant required up to 10 minutes to insert and 1 hour to remove.8
Because only 1 rod is implanted, there is no risk of dislocating previously placed capsules.9 Nor is it necessary, as it was with Norplant, to create channels under the skin, which made implants difficult to palpate after insertion.
Finally, ethylene vinyl acetate, the plastic from which Implanon is made, is less likely than Norplant’s Silastic to form a fibrous sheath that can prolong removal.10
Pharmacology of Implanon
Implanon is a single nonbiodegradable rod of 40% ethylene vinyl acetate and 60% ENG (40 mm×2 mm) covered with a membrane of rate-controlling ethylene vinyl acetate 0.06 mm thick.
Bioavailability
The 68 mg of ENG contained in the rod are initially absorbed by the body at a rate of 60 μg per day, slowly declining to 30 μg per day after 2 years.
Peak serum concentrations (266 pg/mL) of ENG are achieved within 1 day after insertion, effectively suppressing ovulation (which requires 90 pg/mL ENG or more).11,12
The steady release of ENG into the circulation avoids first-pass effects on the liver.
The bioavailability of ENG remains nearly 100% throughout 2 years of use. The elimination half-life of ENG is 25 hours, compared with 42 hours for Norplant’s LNG.
Rapid return to ovulation
After removal, serum ENG concentrations become undetectable within 1 week, and ovulation resumes in 94% of women within 3 to 6 weeks after the implant is removed.11,12
Efficacy and safety
Liver enzyme-inducing drugs lower ENG levels
Like other contraceptive steroids, serum levels of ENG are reduced in women taking liver enzyme-inducing drugs such as rifampin, griseofulvin, phenylbutazone, phenytoin, and carbamazepine, as well as anti-HIV protease inhibitors. Pregnancies were reported among Australian women using Implanon along with some of these antiepileptic drugs.13
Equal efficacy in obese women?
The efficacy of the single-rod implant was studied in clinical trials involving 20,648 cycles of use.1 Only 6 pregnancies occurred in this population—2 each in years 1, 2, and 3 of use. None of the women who weighed 154 lb (70 kg) or more became pregnant.12
However, questions remain as to whether the new implant will maintain its high efficacy in obese women, as it has not been studied in women weighing more than 130% of their ideal body weight. Serum levels of ENG are inversely related to body weight and diminish over time, but increased pregnancy rates in obese women have not been reported.
Potential for ectopic pregancy
Suspect ectopic pregnancy in the rare event that a woman becomes pregnant or experiences lower abdominal pain.1 The reason: Pregnancies in women using contraceptive implants are more likely to be ectopic than are pregnancies in the general population. Ovulation is possible in the third year of use, but intrauterine pregnancies are very rare.1
Limited metabolic effects
Published studies indicate that the metabolic effects of the ENG implant are unlikely to be clinically significant, including its effects on lipid and carbohydrate metabolism, liver function, hemostasis, blood pressure, and thyroid and adrenal function.14-17
Adverse event rates
Overall, implants, including the ENG implant, appear to be safe. The rate of adverse events is comparable to rates in nonusers18 (death, neoplastic disease, cardiovascular events, anemia, hypertension, bone-density changes, diabetes, gall bladder disease, thrombocytopenia, and pelvic inflammatory disease).
Lactation
In a study comparing 42 lactating mother–infant pairs using the ENG implant, compared with 38 pairs using intrauterine devices, there were no significant differences in milk volume, milk constituents, timing and amount of supplementary food, or infant growth rates.19
Because it contains no estrogen, Implanon is a good choice for immediate postpartum contraception.
Insertion and removal
Although the ENG implant is designed to facilitate rapid, simple insertion and removal, clinicians require training in Implanon-specific technique.20 Insertion takes an average of 1 to 2 minutes.21
The disposable trocar comes preloaded,22 and the needle tip has 2 cutting edges with different slopes. The extreme tip has a greater angle and is sharp to allow penetration through the skin. The second upper angle is smaller, and the corresponding edge is unsharpened to reduce the risk of placing the implant in muscle tissue.
Subdermal placement is imperative for efficacy and easy removal.
Insertion technique
Have the patient lie on the examination table with her nondominant arm flexed at the elbow and her hand next to her ear. Identify and mark the insertion site using a sterile marker, and apply any necessary local anesthetic. The insertion site should be 6 to 8 cm above the elbow crease on the inner aspect of the arm. Also mark the skin 6 to 8 cm proximal to the first mark; this serves as a guide during insertion.
Remove Implanon from its package and, with the shield still on the needle, confirm the presence of the implant (a white cylinder) within the needle tip. Remove the needle shield, holding the inserter upright to prevent the implant from falling out. Apply countertraction to the skin at the insertion point and, holding the inserter at an angle no greater than 20 degrees, insert the needle tip into the skin with the beveled side up. Lower the inserter to a horizontal position, lifting the skin with the needle tip without removing the tip from the subdermal connective tissue, and insert the needle to its full length.
Next, break the seal of the applicator by pressing the obturator support, and rotate the obturator 90% (in regard to the needle) in either direction. At this point, the insertion process is the opposite of an injection: Hold the obturator in place and retract the cannula.
After insertion, the implant may not be visible but must remain palpable.1
Timing the insertion. Placement should occur at one of the following times:
- For women who have not been using contraception or who have been using a nonhormonal method, insert the implant between days 1 and 5 of menses.
- For women changing from a combination or progestin-only OC, insert the implant any time during pill-taking.
- For women changing from injectable contraception, insert the implant on the date the next injection is scheduled.
- For women using the IUD, insertion can take place at any time.
Additional birth control for 7 days
Advise all women to use an additional barrier method of contraception for 7 days following insertion, unless insertion directly follows an abortion (in which case, no additional contraception is needed).
In all cases, exclude pregnancy before inserting the implant, although there is no evidence that hormonal contraceptives cause birth defects.
Removal technique
The ENG implant can be removed at any time at the woman’s discretion, but will remain effective for 3 years.
Removal requires a 2-mm incision at the distal tip of the implant. The other end of the rod is then pushed until the rod pops out of the incision.9
Mean removal time is 2.6 to 5.4 minutes.22
In rare cases, the ENG implant cannot be found when the time comes for removal, and special procedures, including sonographic determination of location and sonographically guided removal, are required.
Pain, swelling, redness, and hematoma have been reported during insertion and removal.
Because ovulation resumes rapidly following removal, women still desiring contraception should begin another method immediately or have a new rod inserted through the removal incision.
Tell patients to expect altered bleeding
Side effects associated with the ENG implant include menstrual irregularities:
- infrequent bleeding, 26.9%
- amenorrhea, 18.6%
- prolonged bleeding, 15.1%
- frequent bleeding, 7.4%
Other effects include weight gain, 20.7%; acne, 15.3%; breast pain, 9.1%; and headache, 8.5%.8,18
These symptoms rarely provoke discontinuation. Women using any progestin-only method will have changed bleeding patterns; it is estrogen, along with regular progestin withdrawal, that provides predictable uterine bleeding.23,24
A comparison of bleeding patterns in ENG implant users and LNG implant users found a lower mean number of bleeding/spotting days with the former (15.9–19.3 vs 19.4–21.6; P=.0169).25 Because total uterine blood loss is reduced, users of progestin-only contraceptives (as well as OCs) are less likely to be anemic.
The same comparison25 found that users of ENG implants had more variable bleeding patterns than users of LNG implants. Unfortunately, it is impossible to predict which patterns a woman is likely to experience.
The ENG implant reduced or eliminated menstrual pain in 88% of women who previously experienced dysmenorrhea; pain increased in only 2% of ENG implant users.18
Most women liked the implant
Despite side effects and the need for a physician to insert and remove the implants, most women are satisfied with the method, citing its long duration, convenience, and high efficacy.26,27
Discontinuation rates
Nevertheless, some women do choose to discontinue the method before 3 years are up. Discontinuation rates range from 30.2% in Europe and Canada to 0.9% in Southeast Asia.18,22 Bleeding irregularities are the most commonly cited reason for discontinuation, as they were for Norplant.
A meta-analysis of 13 studies published between 1989 and 1992 found that, among 1,716 women using the ENG implant, 5.3% discontinued in months 1 to 6, 6.4% discontinued in months 7 to 12, 4.1% discontinued in months 13 to 18, and 2.8% discontinued in months 19 to 24. Overall, 82% of women continued to use the ENG implant for up to 24 months.8
Lack of training, lack of counseling, lack of success
When the ENG implant was introduced in Australia in 2001, an unexpectedly high number of unintended pregnancies were reported: 100 pregnancies during the first 18 months.13 Almost universally, these events were traced to improper insertion by untrained clinicians, as well as poor patient selection, timing, and counseling.
In response, the Royal Australian College of General Practitioners developed policies for adequate documentation of proper insertion procedures and patient education. The problems disappeared.13
Preinsertion counseling and postinsertion follow-up are essential for continued use of implants because they increase the patient’s satisfaction with the method and help minimize costly removals.
What to advise patients30
- Strongly stress the likelihood of changes in bleeding patterns
- Lack of inherent protection against sexually transmitted infections, and importance of protective measures (though the implant likely reduces the risk of pelvic inflammatory disease)
- User-specific lifestyle and health advice, such as the need for supplemental contraception in some women during the first 7 days of use
- Pros and cons of implants compared with other methods
- The date when removal is indicated1
Consent form
The patient should sign a consent form, which should be included in her medical record.
Extensive, worldwide experience
Already the 6-capsule and 2-rod LNG implants and the single-rod ENG implant have been used successfully by millions of women. The benefits are high efficacy, long duration, absence of estrogen, ease of use, reversibility, and safety.
Dr. Darney reports that he is a consultant to Organon and a speaker for Barr Laboratories, Berlex, and Organon.
1. Implanon [package insert]. Roseland, NJ: Organon; 2006.
2. Trussell J, Leveque JA, Koenig JD, et al. The economic value of contraception: a comparison of 15 methods. Am J Public Health. 1995;85:494-503.
3. Diaz S, Pavez M, Cardenas H, Croxatto HB. Recovery of fertility and outcome of planned pregnancies after the removal of Norplant subdermal implants or copper-T IUDs. Contraception. 1987;35:569-579.
4. Sivin I, Mishell DR, Jr, Darney P, Wan L, Christ M. Levonorgestrel capsule implants in the United States: a 5-year study. Obstet Gynecol. 1998;92:337-344.
5. Kuiper H, Miller S, Martinez E, Loeb L, Darney PD. Urban adolescent females’ views on the implant and contraceptive decisionmaking: a double paradox. Fam Plann Perspect. 1997;29:167-172.
6. Fu H, Darroch JE, Haas T, Ranjit N. Contraceptive failure rates: new estimates from the 1995 National Survey of Family Growth. Fam Plann Perspect. 1999;31:56-63.
7. Meirik O, Farley TMM, Sivin I, for the International Collaborative Post-Marketing Surveillance of Norplant. Safety and efficacy of levonorgestrel implant, intrauterine device, and sterilization. Am J Obstet Gynecol. 2001;97:539.-
8. Croxatto HB, Urbancsek J, Massai R, Coelingh Bennink H, van Beek A. A multicentre efficacy and safety study of the single contraceptive implant Implanon. Implanon Study Group. Hum Reprod. 1999;14:976-981.
9. Zieman M, Klaisle C, Walker D, Bahisteri E, Darney P. Fingers versus instruments for removing levonorgestrel contraceptive implants (Norplant). J Gynecol Tech. 1997;3:213.-
10. Meckstroth K, Darney PD. Implantable contraception. Obstet Gynecol Clin North Am. 2000;27:781-815.
11. Markarainen L, van Beek A, Tuomiyaara L, Asplund B, Bennink HC. Ovarian function during the use of a single contraceptive implant (Implanon) compared with Norplant. Fertil Steril. 1998;69:714-721.
12. Croxatto HB, Mäkäräinen L. The pharmacodynamics and efficacy of Implanon. Contraception. 1998;58:91S-97S.
13. Harrison-Woolrych M, Hill R. Unintended pregnancies with the etonogestrel implant (Implanon): a case series from post-marketing experience in Australia. Contraception. 2005;71:306-308.
14. Mascarenhas L, van Beek A, Bennink H, Newton J. Twenty-four month comparison of apolipoproteins A-1, A-II and B in contraceptive implant users (Norplant and Implanon) in Birmingham, United Kingdom. Contraception. 1998;58:215-219.
15. Biswas A, Viegas OA, Bennink HJ, Korver T, Ratnam SS. Effect of Implanon use on selected parameters of thyroid and adrenal function. Contraception. 2000;62:247-251.
16. Biswas A, Viegas OA, Coeling Bennink JH, Korver T, Ratnam SS. Implanon contraceptive implants: effects on carbohydrate metabolism. Contraception. 2001;63:137-141.
17. Biswas A, Viegas OA, Roy AC. Effect of Implanon and Norplant subdermal contraceptive implants on serum lipids-a randomized comparative study. Contraception. 2003;68:189-193.
18. Rekers H, Affandi B. Implanon studies conducted in Indonesia. Contraception. 2004;70:433.-
19. Reinprayoon D, Taneepanichskul S, Bunyavejchevin S, et al. Effects of the etonogestrel-releasing contraceptive implant (Implanon) on parameters of breastfeeding compared to those of an intrauterine device. Contraception. 2000;62:239-246.
20. Bromham DR, Davey A, Gaffikin L, Ajello CA. Materials, methods and results of the Norplant training program. Br J Fam Plann. 1995;10:256.-
21. Mascarenhas L. Insertion and removal of Implanon: practical considerations. Eur J Contracept Reprod Health Care. 2000;5(suppl 2):29.-
22. Smith A, Reuter S. An assessment of the use of Implanon in three community services. J Fam Plann Reprod Health Care. 2002;28:193-196.
23. Darney PD, Taylor RN, Klaisle C, Bottles K, Zaloudek C. Serum concentrations of estradiol, progesterone, and levonorgestrel are not determinants of endometrial histology or abnormal bleeding in long-term Norplant implant users. Contraception. 1996;53:97-100.
24. Alvarez-Sanchez F, Brache V, Thevenin F, Cochon L, Faundes A. Hormonal treatment for bleeding irregularities in Norplant implant users. Am J Obstet Gynecol. 1996;174:919-922.
25. Zheng S-R, Zheng H-M, Qian S-Z, Sang G-W, Kaper RF. A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant. Contraception. 1999;60:1-8.
26. Darney PD, Atkinson E, Tanner S, et al. Acceptance and perceptions of Norplant among users in San Francisco, USA. Stud Fam Plann. 1990;21:152-160.
27. Darney PD, Callegari LS, Swift A, Atkinson ES, Robert AM. Condom practices of urban teens using Norplant contraceptive implants, oral contraceptives, and condoms for contraception. Am J Obstet Gynecol. 1999;180:929-937.
28. Shaaban MM, Salem HT, Abdullah KA. Influence of levonorgestrel contraceptive implants, Norplant, initiated early postpartum, upon lactation and infant growth. Contraception. 1985;32:623-635.
29. Brache V, Faundes A, Johansson E, Alvarez F. Anovulation, inadequate luteal phase, and poor sperm penetration in cervical mucus during prolonged use of Norplant implants. Contraception. 1985;31:261-273.
30. Funk S, Miller MM, Mishell DR, Jr, et al. Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel. Contraception. 2005;71:319-326.
Philip D. Darney, MD, MSc
Professor and Chief, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California-San Francisco, San Francisco General Hospital
Philip D. Darney, MD, MSc
Professor and Chief, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California-San Francisco, San Francisco General Hospital
Philip D. Darney, MD, MSc
Professor and Chief, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California-San Francisco, San Francisco General Hospital
On July 17, the US Food and Drug Administration (FDA) approved what may be the most effective hormonal contraceptive ever developed, a single-rod implant that goes by the trade name Implanon. The implant contains 68 mg of etonogestrel (ENG), the active metabolite of desogestrel, in a membrane of ethylene vinyl acetate. In clinical trials involving 20,648 cycles of exposure, only 6 pregnancies occurred, for a cumulative Pearl Index of 0.38 per 100 woman-years.1
This article reviews:
- the 2 contraceptive mechanisms
- indications and patient selection
- pharmacology, safety, adverse effects
- patient satisfaction and discontinuation rates
- insertion and removal
- key points of patient counseling
Unlike Norplant, a multi-rod implant which garnered a million American users before it was removed from the market, the single-rod implant is easy to insert and remove. Before you can order the implant, you must complete a manufacturer-sponsored training program.
Which patients are suitable candidates?
Because the subdermal implant contains only progestin, provides up to 3 years of protection, and requires no daily, weekly, or even monthly action on the part of the user, it is well-suited for:
- Women who wish to or need to avoid estrogen
- Teens who find adherence to a contraceptive regimen difficult
- Healthy adult women who desire long-term protection
- Women who are breastfeeding
Pros and cons
Advantages include:
- Cost. A study2 of 15 contraceptive methods found the implant cost-effective compared to short-acting methods, provided it was used long-term. As of press time, the manufacturer had not released the price.
- Short fertility-recovery time.
- No serious cardiovascular effects.3
Drawbacks. Progestin-only contraceptives also have disadvantages:
- Implants require a minor surgical procedure by trained clinicians for insertion and removal.
- Cost-effectiveness depends on duration of use; early discontinuation negates this benefit.2
- The implant does not protect against sexually transmitted infections—this is a disadvantage of all contraceptive methods except condoms and, perhaps, other barrier methods.
After Implanon is inserted just below the dermis 6 to 8 cm above the elbow crease on the inner aspect of the arm, it remains effective for up to 3 years. To remove it, make a 2-mm incision at the distal tip of the implant and push on the other end of the rod until it pops out.
The implant resides beneath the dermis but above the subcutaneous fat. It remains palpable but invisible, releasing about 60 μg of etonogestrel per day
Images: Rich Larocco
The Norplant experience
Research and development of progestin-only subdermal implants began more than 35 years ago, but early research involving very-low-dose implants found that they did not prevent ectopic pregnancies. This problem ended with Norplant, a 6-capsule implant using the potent progestin levonorgestrel (LNG).
Norplant was highly effective. Over 7 years of use, fewer than 1% of women became pregnant.4 Despite low pregnancy rates and few serious side effects, limitations in component supplies and negative media coverage on complications with removal led to its withdrawal in 2002, leaving no implant available in the US.5
The antiestrogenic effect
Long-acting, progestin-only contraceptives such as the new implant, the LNG-releasing intrauterine system (Mirena), and injectable methods (Depo-Provera) are safer than oral contraceptives (OCs) because they lack estrogen, which can provoke deep venous thrombosis.6,7
LNG, the gonane progestin used in Norplant, binds with high affinity to the progesterone, androgen, mineralocorticoid, and glucocorticoid receptors, but not to estrogen receptors. ENG, also known as 3-keto-desogestrel, demonstrates no estrogenic, anti-inflammatory, or mineralocorticoid activity, but has shown weak androgenic and anabolic activity, as well as strong antiestrogenic activity.
Unlike LNG, which binds mainly to sex hormone-binding globulin, ENG binds mainly to albumin, which is not affected by varying endogenous or exogenous estradiol levels. The safety of ENG has been demonstrated in studies of combined estrogen-progestin OCs and progestin-only OCs that use desogestrel as a component.
The progestin-only implant has 2 primary mechanisms:
- Inhibition of ovulation
- Restriction of sperm penetration of cervical mucus28
Ovulation is suppressed. LNG implants disrupt follicular growth and inhibit ovulation by exerting negative feedback on the hypothalamic–pituitary axis, causing a variety of changes, from anovulation to insufficient luteal function. A few women using LNG implants have quiescent ovaries, but most begin to ovulate as LNG blood concentrations gradually fall.29 The ENG implant suppresses ovulation by altering the hypothalamic–pituitary–ovarian axis and down-regulating the luteinizing hormone surge, which is required to support the production, growth, and maturation of ovarian follicles.11
Oocytes are not fertilized, even if follicles grow during use of the progestin implant. If the follicle ruptures, abnormalities of the ovulatory process prevent release of a viable egg.
Sperm cannot penetrate the cervical mucus. The antiestrogenic action of the progestin renders the cervical mucus viscous, scanty, and impenetrable by sperm.12
Contraceptive effects occur before fertilization
No signs of embryonic development have been found among implant users, indicating the implant lacks abortifacient properties.
Desogestrel in combination with ethinyl estradiol may slightly increase the attributable risk of deep venous thrombosis, but this response has not been shown without estrogen.
Design features
The single-rod design means little discomfort for patients at insertion or removal, an unobtrusive implant, and almost no scarring. Insertion and removal are predictably brief. In US and European trials, which began 10 years ago, average insertion time was 1 minute, and removal time was 3 minutes. In contrast, Norplant required up to 10 minutes to insert and 1 hour to remove.8
Because only 1 rod is implanted, there is no risk of dislocating previously placed capsules.9 Nor is it necessary, as it was with Norplant, to create channels under the skin, which made implants difficult to palpate after insertion.
Finally, ethylene vinyl acetate, the plastic from which Implanon is made, is less likely than Norplant’s Silastic to form a fibrous sheath that can prolong removal.10
Pharmacology of Implanon
Implanon is a single nonbiodegradable rod of 40% ethylene vinyl acetate and 60% ENG (40 mm×2 mm) covered with a membrane of rate-controlling ethylene vinyl acetate 0.06 mm thick.
Bioavailability
The 68 mg of ENG contained in the rod are initially absorbed by the body at a rate of 60 μg per day, slowly declining to 30 μg per day after 2 years.
Peak serum concentrations (266 pg/mL) of ENG are achieved within 1 day after insertion, effectively suppressing ovulation (which requires 90 pg/mL ENG or more).11,12
The steady release of ENG into the circulation avoids first-pass effects on the liver.
The bioavailability of ENG remains nearly 100% throughout 2 years of use. The elimination half-life of ENG is 25 hours, compared with 42 hours for Norplant’s LNG.
Rapid return to ovulation
After removal, serum ENG concentrations become undetectable within 1 week, and ovulation resumes in 94% of women within 3 to 6 weeks after the implant is removed.11,12
Efficacy and safety
Liver enzyme-inducing drugs lower ENG levels
Like other contraceptive steroids, serum levels of ENG are reduced in women taking liver enzyme-inducing drugs such as rifampin, griseofulvin, phenylbutazone, phenytoin, and carbamazepine, as well as anti-HIV protease inhibitors. Pregnancies were reported among Australian women using Implanon along with some of these antiepileptic drugs.13
Equal efficacy in obese women?
The efficacy of the single-rod implant was studied in clinical trials involving 20,648 cycles of use.1 Only 6 pregnancies occurred in this population—2 each in years 1, 2, and 3 of use. None of the women who weighed 154 lb (70 kg) or more became pregnant.12
However, questions remain as to whether the new implant will maintain its high efficacy in obese women, as it has not been studied in women weighing more than 130% of their ideal body weight. Serum levels of ENG are inversely related to body weight and diminish over time, but increased pregnancy rates in obese women have not been reported.
Potential for ectopic pregancy
Suspect ectopic pregnancy in the rare event that a woman becomes pregnant or experiences lower abdominal pain.1 The reason: Pregnancies in women using contraceptive implants are more likely to be ectopic than are pregnancies in the general population. Ovulation is possible in the third year of use, but intrauterine pregnancies are very rare.1
Limited metabolic effects
Published studies indicate that the metabolic effects of the ENG implant are unlikely to be clinically significant, including its effects on lipid and carbohydrate metabolism, liver function, hemostasis, blood pressure, and thyroid and adrenal function.14-17
Adverse event rates
Overall, implants, including the ENG implant, appear to be safe. The rate of adverse events is comparable to rates in nonusers18 (death, neoplastic disease, cardiovascular events, anemia, hypertension, bone-density changes, diabetes, gall bladder disease, thrombocytopenia, and pelvic inflammatory disease).
Lactation
In a study comparing 42 lactating mother–infant pairs using the ENG implant, compared with 38 pairs using intrauterine devices, there were no significant differences in milk volume, milk constituents, timing and amount of supplementary food, or infant growth rates.19
Because it contains no estrogen, Implanon is a good choice for immediate postpartum contraception.
Insertion and removal
Although the ENG implant is designed to facilitate rapid, simple insertion and removal, clinicians require training in Implanon-specific technique.20 Insertion takes an average of 1 to 2 minutes.21
The disposable trocar comes preloaded,22 and the needle tip has 2 cutting edges with different slopes. The extreme tip has a greater angle and is sharp to allow penetration through the skin. The second upper angle is smaller, and the corresponding edge is unsharpened to reduce the risk of placing the implant in muscle tissue.
Subdermal placement is imperative for efficacy and easy removal.
Insertion technique
Have the patient lie on the examination table with her nondominant arm flexed at the elbow and her hand next to her ear. Identify and mark the insertion site using a sterile marker, and apply any necessary local anesthetic. The insertion site should be 6 to 8 cm above the elbow crease on the inner aspect of the arm. Also mark the skin 6 to 8 cm proximal to the first mark; this serves as a guide during insertion.
Remove Implanon from its package and, with the shield still on the needle, confirm the presence of the implant (a white cylinder) within the needle tip. Remove the needle shield, holding the inserter upright to prevent the implant from falling out. Apply countertraction to the skin at the insertion point and, holding the inserter at an angle no greater than 20 degrees, insert the needle tip into the skin with the beveled side up. Lower the inserter to a horizontal position, lifting the skin with the needle tip without removing the tip from the subdermal connective tissue, and insert the needle to its full length.
Next, break the seal of the applicator by pressing the obturator support, and rotate the obturator 90% (in regard to the needle) in either direction. At this point, the insertion process is the opposite of an injection: Hold the obturator in place and retract the cannula.
After insertion, the implant may not be visible but must remain palpable.1
Timing the insertion. Placement should occur at one of the following times:
- For women who have not been using contraception or who have been using a nonhormonal method, insert the implant between days 1 and 5 of menses.
- For women changing from a combination or progestin-only OC, insert the implant any time during pill-taking.
- For women changing from injectable contraception, insert the implant on the date the next injection is scheduled.
- For women using the IUD, insertion can take place at any time.
Additional birth control for 7 days
Advise all women to use an additional barrier method of contraception for 7 days following insertion, unless insertion directly follows an abortion (in which case, no additional contraception is needed).
In all cases, exclude pregnancy before inserting the implant, although there is no evidence that hormonal contraceptives cause birth defects.
Removal technique
The ENG implant can be removed at any time at the woman’s discretion, but will remain effective for 3 years.
Removal requires a 2-mm incision at the distal tip of the implant. The other end of the rod is then pushed until the rod pops out of the incision.9
Mean removal time is 2.6 to 5.4 minutes.22
In rare cases, the ENG implant cannot be found when the time comes for removal, and special procedures, including sonographic determination of location and sonographically guided removal, are required.
Pain, swelling, redness, and hematoma have been reported during insertion and removal.
Because ovulation resumes rapidly following removal, women still desiring contraception should begin another method immediately or have a new rod inserted through the removal incision.
Tell patients to expect altered bleeding
Side effects associated with the ENG implant include menstrual irregularities:
- infrequent bleeding, 26.9%
- amenorrhea, 18.6%
- prolonged bleeding, 15.1%
- frequent bleeding, 7.4%
Other effects include weight gain, 20.7%; acne, 15.3%; breast pain, 9.1%; and headache, 8.5%.8,18
These symptoms rarely provoke discontinuation. Women using any progestin-only method will have changed bleeding patterns; it is estrogen, along with regular progestin withdrawal, that provides predictable uterine bleeding.23,24
A comparison of bleeding patterns in ENG implant users and LNG implant users found a lower mean number of bleeding/spotting days with the former (15.9–19.3 vs 19.4–21.6; P=.0169).25 Because total uterine blood loss is reduced, users of progestin-only contraceptives (as well as OCs) are less likely to be anemic.
The same comparison25 found that users of ENG implants had more variable bleeding patterns than users of LNG implants. Unfortunately, it is impossible to predict which patterns a woman is likely to experience.
The ENG implant reduced or eliminated menstrual pain in 88% of women who previously experienced dysmenorrhea; pain increased in only 2% of ENG implant users.18
Most women liked the implant
Despite side effects and the need for a physician to insert and remove the implants, most women are satisfied with the method, citing its long duration, convenience, and high efficacy.26,27
Discontinuation rates
Nevertheless, some women do choose to discontinue the method before 3 years are up. Discontinuation rates range from 30.2% in Europe and Canada to 0.9% in Southeast Asia.18,22 Bleeding irregularities are the most commonly cited reason for discontinuation, as they were for Norplant.
A meta-analysis of 13 studies published between 1989 and 1992 found that, among 1,716 women using the ENG implant, 5.3% discontinued in months 1 to 6, 6.4% discontinued in months 7 to 12, 4.1% discontinued in months 13 to 18, and 2.8% discontinued in months 19 to 24. Overall, 82% of women continued to use the ENG implant for up to 24 months.8
Lack of training, lack of counseling, lack of success
When the ENG implant was introduced in Australia in 2001, an unexpectedly high number of unintended pregnancies were reported: 100 pregnancies during the first 18 months.13 Almost universally, these events were traced to improper insertion by untrained clinicians, as well as poor patient selection, timing, and counseling.
In response, the Royal Australian College of General Practitioners developed policies for adequate documentation of proper insertion procedures and patient education. The problems disappeared.13
Preinsertion counseling and postinsertion follow-up are essential for continued use of implants because they increase the patient’s satisfaction with the method and help minimize costly removals.
What to advise patients30
- Strongly stress the likelihood of changes in bleeding patterns
- Lack of inherent protection against sexually transmitted infections, and importance of protective measures (though the implant likely reduces the risk of pelvic inflammatory disease)
- User-specific lifestyle and health advice, such as the need for supplemental contraception in some women during the first 7 days of use
- Pros and cons of implants compared with other methods
- The date when removal is indicated1
Consent form
The patient should sign a consent form, which should be included in her medical record.
Extensive, worldwide experience
Already the 6-capsule and 2-rod LNG implants and the single-rod ENG implant have been used successfully by millions of women. The benefits are high efficacy, long duration, absence of estrogen, ease of use, reversibility, and safety.
Dr. Darney reports that he is a consultant to Organon and a speaker for Barr Laboratories, Berlex, and Organon.
On July 17, the US Food and Drug Administration (FDA) approved what may be the most effective hormonal contraceptive ever developed, a single-rod implant that goes by the trade name Implanon. The implant contains 68 mg of etonogestrel (ENG), the active metabolite of desogestrel, in a membrane of ethylene vinyl acetate. In clinical trials involving 20,648 cycles of exposure, only 6 pregnancies occurred, for a cumulative Pearl Index of 0.38 per 100 woman-years.1
This article reviews:
- the 2 contraceptive mechanisms
- indications and patient selection
- pharmacology, safety, adverse effects
- patient satisfaction and discontinuation rates
- insertion and removal
- key points of patient counseling
Unlike Norplant, a multi-rod implant which garnered a million American users before it was removed from the market, the single-rod implant is easy to insert and remove. Before you can order the implant, you must complete a manufacturer-sponsored training program.
Which patients are suitable candidates?
Because the subdermal implant contains only progestin, provides up to 3 years of protection, and requires no daily, weekly, or even monthly action on the part of the user, it is well-suited for:
- Women who wish to or need to avoid estrogen
- Teens who find adherence to a contraceptive regimen difficult
- Healthy adult women who desire long-term protection
- Women who are breastfeeding
Pros and cons
Advantages include:
- Cost. A study2 of 15 contraceptive methods found the implant cost-effective compared to short-acting methods, provided it was used long-term. As of press time, the manufacturer had not released the price.
- Short fertility-recovery time.
- No serious cardiovascular effects.3
Drawbacks. Progestin-only contraceptives also have disadvantages:
- Implants require a minor surgical procedure by trained clinicians for insertion and removal.
- Cost-effectiveness depends on duration of use; early discontinuation negates this benefit.2
- The implant does not protect against sexually transmitted infections—this is a disadvantage of all contraceptive methods except condoms and, perhaps, other barrier methods.
After Implanon is inserted just below the dermis 6 to 8 cm above the elbow crease on the inner aspect of the arm, it remains effective for up to 3 years. To remove it, make a 2-mm incision at the distal tip of the implant and push on the other end of the rod until it pops out.
The implant resides beneath the dermis but above the subcutaneous fat. It remains palpable but invisible, releasing about 60 μg of etonogestrel per day
Images: Rich Larocco
The Norplant experience
Research and development of progestin-only subdermal implants began more than 35 years ago, but early research involving very-low-dose implants found that they did not prevent ectopic pregnancies. This problem ended with Norplant, a 6-capsule implant using the potent progestin levonorgestrel (LNG).
Norplant was highly effective. Over 7 years of use, fewer than 1% of women became pregnant.4 Despite low pregnancy rates and few serious side effects, limitations in component supplies and negative media coverage on complications with removal led to its withdrawal in 2002, leaving no implant available in the US.5
The antiestrogenic effect
Long-acting, progestin-only contraceptives such as the new implant, the LNG-releasing intrauterine system (Mirena), and injectable methods (Depo-Provera) are safer than oral contraceptives (OCs) because they lack estrogen, which can provoke deep venous thrombosis.6,7
LNG, the gonane progestin used in Norplant, binds with high affinity to the progesterone, androgen, mineralocorticoid, and glucocorticoid receptors, but not to estrogen receptors. ENG, also known as 3-keto-desogestrel, demonstrates no estrogenic, anti-inflammatory, or mineralocorticoid activity, but has shown weak androgenic and anabolic activity, as well as strong antiestrogenic activity.
Unlike LNG, which binds mainly to sex hormone-binding globulin, ENG binds mainly to albumin, which is not affected by varying endogenous or exogenous estradiol levels. The safety of ENG has been demonstrated in studies of combined estrogen-progestin OCs and progestin-only OCs that use desogestrel as a component.
The progestin-only implant has 2 primary mechanisms:
- Inhibition of ovulation
- Restriction of sperm penetration of cervical mucus28
Ovulation is suppressed. LNG implants disrupt follicular growth and inhibit ovulation by exerting negative feedback on the hypothalamic–pituitary axis, causing a variety of changes, from anovulation to insufficient luteal function. A few women using LNG implants have quiescent ovaries, but most begin to ovulate as LNG blood concentrations gradually fall.29 The ENG implant suppresses ovulation by altering the hypothalamic–pituitary–ovarian axis and down-regulating the luteinizing hormone surge, which is required to support the production, growth, and maturation of ovarian follicles.11
Oocytes are not fertilized, even if follicles grow during use of the progestin implant. If the follicle ruptures, abnormalities of the ovulatory process prevent release of a viable egg.
Sperm cannot penetrate the cervical mucus. The antiestrogenic action of the progestin renders the cervical mucus viscous, scanty, and impenetrable by sperm.12
Contraceptive effects occur before fertilization
No signs of embryonic development have been found among implant users, indicating the implant lacks abortifacient properties.
Desogestrel in combination with ethinyl estradiol may slightly increase the attributable risk of deep venous thrombosis, but this response has not been shown without estrogen.
Design features
The single-rod design means little discomfort for patients at insertion or removal, an unobtrusive implant, and almost no scarring. Insertion and removal are predictably brief. In US and European trials, which began 10 years ago, average insertion time was 1 minute, and removal time was 3 minutes. In contrast, Norplant required up to 10 minutes to insert and 1 hour to remove.8
Because only 1 rod is implanted, there is no risk of dislocating previously placed capsules.9 Nor is it necessary, as it was with Norplant, to create channels under the skin, which made implants difficult to palpate after insertion.
Finally, ethylene vinyl acetate, the plastic from which Implanon is made, is less likely than Norplant’s Silastic to form a fibrous sheath that can prolong removal.10
Pharmacology of Implanon
Implanon is a single nonbiodegradable rod of 40% ethylene vinyl acetate and 60% ENG (40 mm×2 mm) covered with a membrane of rate-controlling ethylene vinyl acetate 0.06 mm thick.
Bioavailability
The 68 mg of ENG contained in the rod are initially absorbed by the body at a rate of 60 μg per day, slowly declining to 30 μg per day after 2 years.
Peak serum concentrations (266 pg/mL) of ENG are achieved within 1 day after insertion, effectively suppressing ovulation (which requires 90 pg/mL ENG or more).11,12
The steady release of ENG into the circulation avoids first-pass effects on the liver.
The bioavailability of ENG remains nearly 100% throughout 2 years of use. The elimination half-life of ENG is 25 hours, compared with 42 hours for Norplant’s LNG.
Rapid return to ovulation
After removal, serum ENG concentrations become undetectable within 1 week, and ovulation resumes in 94% of women within 3 to 6 weeks after the implant is removed.11,12
Efficacy and safety
Liver enzyme-inducing drugs lower ENG levels
Like other contraceptive steroids, serum levels of ENG are reduced in women taking liver enzyme-inducing drugs such as rifampin, griseofulvin, phenylbutazone, phenytoin, and carbamazepine, as well as anti-HIV protease inhibitors. Pregnancies were reported among Australian women using Implanon along with some of these antiepileptic drugs.13
Equal efficacy in obese women?
The efficacy of the single-rod implant was studied in clinical trials involving 20,648 cycles of use.1 Only 6 pregnancies occurred in this population—2 each in years 1, 2, and 3 of use. None of the women who weighed 154 lb (70 kg) or more became pregnant.12
However, questions remain as to whether the new implant will maintain its high efficacy in obese women, as it has not been studied in women weighing more than 130% of their ideal body weight. Serum levels of ENG are inversely related to body weight and diminish over time, but increased pregnancy rates in obese women have not been reported.
Potential for ectopic pregancy
Suspect ectopic pregnancy in the rare event that a woman becomes pregnant or experiences lower abdominal pain.1 The reason: Pregnancies in women using contraceptive implants are more likely to be ectopic than are pregnancies in the general population. Ovulation is possible in the third year of use, but intrauterine pregnancies are very rare.1
Limited metabolic effects
Published studies indicate that the metabolic effects of the ENG implant are unlikely to be clinically significant, including its effects on lipid and carbohydrate metabolism, liver function, hemostasis, blood pressure, and thyroid and adrenal function.14-17
Adverse event rates
Overall, implants, including the ENG implant, appear to be safe. The rate of adverse events is comparable to rates in nonusers18 (death, neoplastic disease, cardiovascular events, anemia, hypertension, bone-density changes, diabetes, gall bladder disease, thrombocytopenia, and pelvic inflammatory disease).
Lactation
In a study comparing 42 lactating mother–infant pairs using the ENG implant, compared with 38 pairs using intrauterine devices, there were no significant differences in milk volume, milk constituents, timing and amount of supplementary food, or infant growth rates.19
Because it contains no estrogen, Implanon is a good choice for immediate postpartum contraception.
Insertion and removal
Although the ENG implant is designed to facilitate rapid, simple insertion and removal, clinicians require training in Implanon-specific technique.20 Insertion takes an average of 1 to 2 minutes.21
The disposable trocar comes preloaded,22 and the needle tip has 2 cutting edges with different slopes. The extreme tip has a greater angle and is sharp to allow penetration through the skin. The second upper angle is smaller, and the corresponding edge is unsharpened to reduce the risk of placing the implant in muscle tissue.
Subdermal placement is imperative for efficacy and easy removal.
Insertion technique
Have the patient lie on the examination table with her nondominant arm flexed at the elbow and her hand next to her ear. Identify and mark the insertion site using a sterile marker, and apply any necessary local anesthetic. The insertion site should be 6 to 8 cm above the elbow crease on the inner aspect of the arm. Also mark the skin 6 to 8 cm proximal to the first mark; this serves as a guide during insertion.
Remove Implanon from its package and, with the shield still on the needle, confirm the presence of the implant (a white cylinder) within the needle tip. Remove the needle shield, holding the inserter upright to prevent the implant from falling out. Apply countertraction to the skin at the insertion point and, holding the inserter at an angle no greater than 20 degrees, insert the needle tip into the skin with the beveled side up. Lower the inserter to a horizontal position, lifting the skin with the needle tip without removing the tip from the subdermal connective tissue, and insert the needle to its full length.
Next, break the seal of the applicator by pressing the obturator support, and rotate the obturator 90% (in regard to the needle) in either direction. At this point, the insertion process is the opposite of an injection: Hold the obturator in place and retract the cannula.
After insertion, the implant may not be visible but must remain palpable.1
Timing the insertion. Placement should occur at one of the following times:
- For women who have not been using contraception or who have been using a nonhormonal method, insert the implant between days 1 and 5 of menses.
- For women changing from a combination or progestin-only OC, insert the implant any time during pill-taking.
- For women changing from injectable contraception, insert the implant on the date the next injection is scheduled.
- For women using the IUD, insertion can take place at any time.
Additional birth control for 7 days
Advise all women to use an additional barrier method of contraception for 7 days following insertion, unless insertion directly follows an abortion (in which case, no additional contraception is needed).
In all cases, exclude pregnancy before inserting the implant, although there is no evidence that hormonal contraceptives cause birth defects.
Removal technique
The ENG implant can be removed at any time at the woman’s discretion, but will remain effective for 3 years.
Removal requires a 2-mm incision at the distal tip of the implant. The other end of the rod is then pushed until the rod pops out of the incision.9
Mean removal time is 2.6 to 5.4 minutes.22
In rare cases, the ENG implant cannot be found when the time comes for removal, and special procedures, including sonographic determination of location and sonographically guided removal, are required.
Pain, swelling, redness, and hematoma have been reported during insertion and removal.
Because ovulation resumes rapidly following removal, women still desiring contraception should begin another method immediately or have a new rod inserted through the removal incision.
Tell patients to expect altered bleeding
Side effects associated with the ENG implant include menstrual irregularities:
- infrequent bleeding, 26.9%
- amenorrhea, 18.6%
- prolonged bleeding, 15.1%
- frequent bleeding, 7.4%
Other effects include weight gain, 20.7%; acne, 15.3%; breast pain, 9.1%; and headache, 8.5%.8,18
These symptoms rarely provoke discontinuation. Women using any progestin-only method will have changed bleeding patterns; it is estrogen, along with regular progestin withdrawal, that provides predictable uterine bleeding.23,24
A comparison of bleeding patterns in ENG implant users and LNG implant users found a lower mean number of bleeding/spotting days with the former (15.9–19.3 vs 19.4–21.6; P=.0169).25 Because total uterine blood loss is reduced, users of progestin-only contraceptives (as well as OCs) are less likely to be anemic.
The same comparison25 found that users of ENG implants had more variable bleeding patterns than users of LNG implants. Unfortunately, it is impossible to predict which patterns a woman is likely to experience.
The ENG implant reduced or eliminated menstrual pain in 88% of women who previously experienced dysmenorrhea; pain increased in only 2% of ENG implant users.18
Most women liked the implant
Despite side effects and the need for a physician to insert and remove the implants, most women are satisfied with the method, citing its long duration, convenience, and high efficacy.26,27
Discontinuation rates
Nevertheless, some women do choose to discontinue the method before 3 years are up. Discontinuation rates range from 30.2% in Europe and Canada to 0.9% in Southeast Asia.18,22 Bleeding irregularities are the most commonly cited reason for discontinuation, as they were for Norplant.
A meta-analysis of 13 studies published between 1989 and 1992 found that, among 1,716 women using the ENG implant, 5.3% discontinued in months 1 to 6, 6.4% discontinued in months 7 to 12, 4.1% discontinued in months 13 to 18, and 2.8% discontinued in months 19 to 24. Overall, 82% of women continued to use the ENG implant for up to 24 months.8
Lack of training, lack of counseling, lack of success
When the ENG implant was introduced in Australia in 2001, an unexpectedly high number of unintended pregnancies were reported: 100 pregnancies during the first 18 months.13 Almost universally, these events were traced to improper insertion by untrained clinicians, as well as poor patient selection, timing, and counseling.
In response, the Royal Australian College of General Practitioners developed policies for adequate documentation of proper insertion procedures and patient education. The problems disappeared.13
Preinsertion counseling and postinsertion follow-up are essential for continued use of implants because they increase the patient’s satisfaction with the method and help minimize costly removals.
What to advise patients30
- Strongly stress the likelihood of changes in bleeding patterns
- Lack of inherent protection against sexually transmitted infections, and importance of protective measures (though the implant likely reduces the risk of pelvic inflammatory disease)
- User-specific lifestyle and health advice, such as the need for supplemental contraception in some women during the first 7 days of use
- Pros and cons of implants compared with other methods
- The date when removal is indicated1
Consent form
The patient should sign a consent form, which should be included in her medical record.
Extensive, worldwide experience
Already the 6-capsule and 2-rod LNG implants and the single-rod ENG implant have been used successfully by millions of women. The benefits are high efficacy, long duration, absence of estrogen, ease of use, reversibility, and safety.
Dr. Darney reports that he is a consultant to Organon and a speaker for Barr Laboratories, Berlex, and Organon.
1. Implanon [package insert]. Roseland, NJ: Organon; 2006.
2. Trussell J, Leveque JA, Koenig JD, et al. The economic value of contraception: a comparison of 15 methods. Am J Public Health. 1995;85:494-503.
3. Diaz S, Pavez M, Cardenas H, Croxatto HB. Recovery of fertility and outcome of planned pregnancies after the removal of Norplant subdermal implants or copper-T IUDs. Contraception. 1987;35:569-579.
4. Sivin I, Mishell DR, Jr, Darney P, Wan L, Christ M. Levonorgestrel capsule implants in the United States: a 5-year study. Obstet Gynecol. 1998;92:337-344.
5. Kuiper H, Miller S, Martinez E, Loeb L, Darney PD. Urban adolescent females’ views on the implant and contraceptive decisionmaking: a double paradox. Fam Plann Perspect. 1997;29:167-172.
6. Fu H, Darroch JE, Haas T, Ranjit N. Contraceptive failure rates: new estimates from the 1995 National Survey of Family Growth. Fam Plann Perspect. 1999;31:56-63.
7. Meirik O, Farley TMM, Sivin I, for the International Collaborative Post-Marketing Surveillance of Norplant. Safety and efficacy of levonorgestrel implant, intrauterine device, and sterilization. Am J Obstet Gynecol. 2001;97:539.-
8. Croxatto HB, Urbancsek J, Massai R, Coelingh Bennink H, van Beek A. A multicentre efficacy and safety study of the single contraceptive implant Implanon. Implanon Study Group. Hum Reprod. 1999;14:976-981.
9. Zieman M, Klaisle C, Walker D, Bahisteri E, Darney P. Fingers versus instruments for removing levonorgestrel contraceptive implants (Norplant). J Gynecol Tech. 1997;3:213.-
10. Meckstroth K, Darney PD. Implantable contraception. Obstet Gynecol Clin North Am. 2000;27:781-815.
11. Markarainen L, van Beek A, Tuomiyaara L, Asplund B, Bennink HC. Ovarian function during the use of a single contraceptive implant (Implanon) compared with Norplant. Fertil Steril. 1998;69:714-721.
12. Croxatto HB, Mäkäräinen L. The pharmacodynamics and efficacy of Implanon. Contraception. 1998;58:91S-97S.
13. Harrison-Woolrych M, Hill R. Unintended pregnancies with the etonogestrel implant (Implanon): a case series from post-marketing experience in Australia. Contraception. 2005;71:306-308.
14. Mascarenhas L, van Beek A, Bennink H, Newton J. Twenty-four month comparison of apolipoproteins A-1, A-II and B in contraceptive implant users (Norplant and Implanon) in Birmingham, United Kingdom. Contraception. 1998;58:215-219.
15. Biswas A, Viegas OA, Bennink HJ, Korver T, Ratnam SS. Effect of Implanon use on selected parameters of thyroid and adrenal function. Contraception. 2000;62:247-251.
16. Biswas A, Viegas OA, Coeling Bennink JH, Korver T, Ratnam SS. Implanon contraceptive implants: effects on carbohydrate metabolism. Contraception. 2001;63:137-141.
17. Biswas A, Viegas OA, Roy AC. Effect of Implanon and Norplant subdermal contraceptive implants on serum lipids-a randomized comparative study. Contraception. 2003;68:189-193.
18. Rekers H, Affandi B. Implanon studies conducted in Indonesia. Contraception. 2004;70:433.-
19. Reinprayoon D, Taneepanichskul S, Bunyavejchevin S, et al. Effects of the etonogestrel-releasing contraceptive implant (Implanon) on parameters of breastfeeding compared to those of an intrauterine device. Contraception. 2000;62:239-246.
20. Bromham DR, Davey A, Gaffikin L, Ajello CA. Materials, methods and results of the Norplant training program. Br J Fam Plann. 1995;10:256.-
21. Mascarenhas L. Insertion and removal of Implanon: practical considerations. Eur J Contracept Reprod Health Care. 2000;5(suppl 2):29.-
22. Smith A, Reuter S. An assessment of the use of Implanon in three community services. J Fam Plann Reprod Health Care. 2002;28:193-196.
23. Darney PD, Taylor RN, Klaisle C, Bottles K, Zaloudek C. Serum concentrations of estradiol, progesterone, and levonorgestrel are not determinants of endometrial histology or abnormal bleeding in long-term Norplant implant users. Contraception. 1996;53:97-100.
24. Alvarez-Sanchez F, Brache V, Thevenin F, Cochon L, Faundes A. Hormonal treatment for bleeding irregularities in Norplant implant users. Am J Obstet Gynecol. 1996;174:919-922.
25. Zheng S-R, Zheng H-M, Qian S-Z, Sang G-W, Kaper RF. A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant. Contraception. 1999;60:1-8.
26. Darney PD, Atkinson E, Tanner S, et al. Acceptance and perceptions of Norplant among users in San Francisco, USA. Stud Fam Plann. 1990;21:152-160.
27. Darney PD, Callegari LS, Swift A, Atkinson ES, Robert AM. Condom practices of urban teens using Norplant contraceptive implants, oral contraceptives, and condoms for contraception. Am J Obstet Gynecol. 1999;180:929-937.
28. Shaaban MM, Salem HT, Abdullah KA. Influence of levonorgestrel contraceptive implants, Norplant, initiated early postpartum, upon lactation and infant growth. Contraception. 1985;32:623-635.
29. Brache V, Faundes A, Johansson E, Alvarez F. Anovulation, inadequate luteal phase, and poor sperm penetration in cervical mucus during prolonged use of Norplant implants. Contraception. 1985;31:261-273.
30. Funk S, Miller MM, Mishell DR, Jr, et al. Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel. Contraception. 2005;71:319-326.
1. Implanon [package insert]. Roseland, NJ: Organon; 2006.
2. Trussell J, Leveque JA, Koenig JD, et al. The economic value of contraception: a comparison of 15 methods. Am J Public Health. 1995;85:494-503.
3. Diaz S, Pavez M, Cardenas H, Croxatto HB. Recovery of fertility and outcome of planned pregnancies after the removal of Norplant subdermal implants or copper-T IUDs. Contraception. 1987;35:569-579.
4. Sivin I, Mishell DR, Jr, Darney P, Wan L, Christ M. Levonorgestrel capsule implants in the United States: a 5-year study. Obstet Gynecol. 1998;92:337-344.
5. Kuiper H, Miller S, Martinez E, Loeb L, Darney PD. Urban adolescent females’ views on the implant and contraceptive decisionmaking: a double paradox. Fam Plann Perspect. 1997;29:167-172.
6. Fu H, Darroch JE, Haas T, Ranjit N. Contraceptive failure rates: new estimates from the 1995 National Survey of Family Growth. Fam Plann Perspect. 1999;31:56-63.
7. Meirik O, Farley TMM, Sivin I, for the International Collaborative Post-Marketing Surveillance of Norplant. Safety and efficacy of levonorgestrel implant, intrauterine device, and sterilization. Am J Obstet Gynecol. 2001;97:539.-
8. Croxatto HB, Urbancsek J, Massai R, Coelingh Bennink H, van Beek A. A multicentre efficacy and safety study of the single contraceptive implant Implanon. Implanon Study Group. Hum Reprod. 1999;14:976-981.
9. Zieman M, Klaisle C, Walker D, Bahisteri E, Darney P. Fingers versus instruments for removing levonorgestrel contraceptive implants (Norplant). J Gynecol Tech. 1997;3:213.-
10. Meckstroth K, Darney PD. Implantable contraception. Obstet Gynecol Clin North Am. 2000;27:781-815.
11. Markarainen L, van Beek A, Tuomiyaara L, Asplund B, Bennink HC. Ovarian function during the use of a single contraceptive implant (Implanon) compared with Norplant. Fertil Steril. 1998;69:714-721.
12. Croxatto HB, Mäkäräinen L. The pharmacodynamics and efficacy of Implanon. Contraception. 1998;58:91S-97S.
13. Harrison-Woolrych M, Hill R. Unintended pregnancies with the etonogestrel implant (Implanon): a case series from post-marketing experience in Australia. Contraception. 2005;71:306-308.
14. Mascarenhas L, van Beek A, Bennink H, Newton J. Twenty-four month comparison of apolipoproteins A-1, A-II and B in contraceptive implant users (Norplant and Implanon) in Birmingham, United Kingdom. Contraception. 1998;58:215-219.
15. Biswas A, Viegas OA, Bennink HJ, Korver T, Ratnam SS. Effect of Implanon use on selected parameters of thyroid and adrenal function. Contraception. 2000;62:247-251.
16. Biswas A, Viegas OA, Coeling Bennink JH, Korver T, Ratnam SS. Implanon contraceptive implants: effects on carbohydrate metabolism. Contraception. 2001;63:137-141.
17. Biswas A, Viegas OA, Roy AC. Effect of Implanon and Norplant subdermal contraceptive implants on serum lipids-a randomized comparative study. Contraception. 2003;68:189-193.
18. Rekers H, Affandi B. Implanon studies conducted in Indonesia. Contraception. 2004;70:433.-
19. Reinprayoon D, Taneepanichskul S, Bunyavejchevin S, et al. Effects of the etonogestrel-releasing contraceptive implant (Implanon) on parameters of breastfeeding compared to those of an intrauterine device. Contraception. 2000;62:239-246.
20. Bromham DR, Davey A, Gaffikin L, Ajello CA. Materials, methods and results of the Norplant training program. Br J Fam Plann. 1995;10:256.-
21. Mascarenhas L. Insertion and removal of Implanon: practical considerations. Eur J Contracept Reprod Health Care. 2000;5(suppl 2):29.-
22. Smith A, Reuter S. An assessment of the use of Implanon in three community services. J Fam Plann Reprod Health Care. 2002;28:193-196.
23. Darney PD, Taylor RN, Klaisle C, Bottles K, Zaloudek C. Serum concentrations of estradiol, progesterone, and levonorgestrel are not determinants of endometrial histology or abnormal bleeding in long-term Norplant implant users. Contraception. 1996;53:97-100.
24. Alvarez-Sanchez F, Brache V, Thevenin F, Cochon L, Faundes A. Hormonal treatment for bleeding irregularities in Norplant implant users. Am J Obstet Gynecol. 1996;174:919-922.
25. Zheng S-R, Zheng H-M, Qian S-Z, Sang G-W, Kaper RF. A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant. Contraception. 1999;60:1-8.
26. Darney PD, Atkinson E, Tanner S, et al. Acceptance and perceptions of Norplant among users in San Francisco, USA. Stud Fam Plann. 1990;21:152-160.
27. Darney PD, Callegari LS, Swift A, Atkinson ES, Robert AM. Condom practices of urban teens using Norplant contraceptive implants, oral contraceptives, and condoms for contraception. Am J Obstet Gynecol. 1999;180:929-937.
28. Shaaban MM, Salem HT, Abdullah KA. Influence of levonorgestrel contraceptive implants, Norplant, initiated early postpartum, upon lactation and infant growth. Contraception. 1985;32:623-635.
29. Brache V, Faundes A, Johansson E, Alvarez F. Anovulation, inadequate luteal phase, and poor sperm penetration in cervical mucus during prolonged use of Norplant implants. Contraception. 1985;31:261-273.
30. Funk S, Miller MM, Mishell DR, Jr, et al. Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel. Contraception. 2005;71:319-326.