Pelvic Floor Dysfunction

More than one-third of women aged 45 years or older experience uterine prolapse, a condition that can impair physical, psychological, and sexual function. To compare vaginal vault suspension with hysterectomy, investigators at 4 large Dutch teaching hospitals from 2009 to 2012 randomly assigned women with uterine prolapse to sacrospinous hysteropexy (SSLF) or vaginal hysterectomy with uterosacral ligament suspension (ULS). The primary outcome was recurrent stage 2 or greater prolapse (within 1 cm or more of the hymenal ring) with bothersome bulge symptoms or repeat surgery for prolapse by 12 months follow-up.

Details of the trialOne hundred two women assigned to SSLF (median age, 62.7 years) and 100 assigned to hysterectomy with ULS (median age, 
61.9 years) were analyzed for the primary outcome. The patients ranged in age from 33 to 85 years.

Surgical failure rates and adverse events were similarMean hospital stay was 3 days in both groups and the occurrence of urinary retention was likewise similar (15% for SSLF and 11% for hysterectomy with ULS). At 
12 months, 0 and 4 women in the SSLF and hysterectomy with ULS groups, respectively, met the primary outcome. Study participants were considered a “surgical failure” if any type of prolapse with bothersome symptoms or repeat surgery or pessary use occurred. Failures occurred in approximately one-half of the women in both groups.

Rates of serious adverse events were low, and none were related to type of surgery. Nine women experienced buttock pain following SSLF hysteropexy, a known complication of this surgery. This pain resolved within 
6 weeks in 8 of these women. In the remaining woman, persistent pain led to release of the hysteropexy suture and vaginal hysterectomy 4 months after her initial procedure.

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More than one-third of women aged 45 years or older experience uterine prolapse, a condition that can impair physical, psychological, and sexual function. To compare vaginal vault suspension with hysterectomy, investigators at 4 large Dutch teaching hospitals from 2009 to 2012 randomly assigned women with uterine prolapse to sacrospinous hysteropexy (SSLF) or vaginal hysterectomy with uterosacral ligament suspension (ULS). The primary outcome was recurrent stage 2 or greater prolapse (within 1 cm or more of the hymenal ring) with bothersome bulge symptoms or repeat surgery for prolapse by 12 months follow-up.

Details of the trialOne hundred two women assigned to SSLF (median age, 62.7 years) and 100 assigned to hysterectomy with ULS (median age, 
61.9 years) were analyzed for the primary outcome. The patients ranged in age from 33 to 85 years.

Surgical failure rates and adverse events were similarMean hospital stay was 3 days in both groups and the occurrence of urinary retention was likewise similar (15% for SSLF and 11% for hysterectomy with ULS). At 
12 months, 0 and 4 women in the SSLF and hysterectomy with ULS groups, respectively, met the primary outcome. Study participants were considered a “surgical failure” if any type of prolapse with bothersome symptoms or repeat surgery or pessary use occurred. Failures occurred in approximately one-half of the women in both groups.

Rates of serious adverse events were low, and none were related to type of surgery. Nine women experienced buttock pain following SSLF hysteropexy, a known complication of this surgery. This pain resolved within 
6 weeks in 8 of these women. In the remaining woman, persistent pain led to release of the hysteropexy suture and vaginal hysterectomy 4 months after her initial procedure.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

More than one-third of women aged 45 years or older experience uterine prolapse, a condition that can impair physical, psychological, and sexual function. To compare vaginal vault suspension with hysterectomy, investigators at 4 large Dutch teaching hospitals from 2009 to 2012 randomly assigned women with uterine prolapse to sacrospinous hysteropexy (SSLF) or vaginal hysterectomy with uterosacral ligament suspension (ULS). The primary outcome was recurrent stage 2 or greater prolapse (within 1 cm or more of the hymenal ring) with bothersome bulge symptoms or repeat surgery for prolapse by 12 months follow-up.

Details of the trialOne hundred two women assigned to SSLF (median age, 62.7 years) and 100 assigned to hysterectomy with ULS (median age, 
61.9 years) were analyzed for the primary outcome. The patients ranged in age from 33 to 85 years.

Surgical failure rates and adverse events were similarMean hospital stay was 3 days in both groups and the occurrence of urinary retention was likewise similar (15% for SSLF and 11% for hysterectomy with ULS). At 
12 months, 0 and 4 women in the SSLF and hysterectomy with ULS groups, respectively, met the primary outcome. Study participants were considered a “surgical failure” if any type of prolapse with bothersome symptoms or repeat surgery or pessary use occurred. Failures occurred in approximately one-half of the women in both groups.

Rates of serious adverse events were low, and none were related to type of surgery. Nine women experienced buttock pain following SSLF hysteropexy, a known complication of this surgery. This pain resolved within 
6 weeks in 8 of these women. In the remaining woman, persistent pain led to release of the hysteropexy suture and vaginal hysterectomy 4 months after her initial procedure.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In an audiocast summarizing his Sunday Lunch Talk at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG) on May 3, 2015, Dr. Michael L. Krychman discusses new treatment options for vulvar and vaginal atrophy (VVA), including over-the-counter and prescription products and procedures. He emphasizes that a better understanding of the physical and anatomic changes in menopause has led to these improved options.

Dr. Krychman also recommends the use of "genitourinary syndrome of menopause" (GSM), new terminology for VVA suggested by the International Society for the Study of Women's Sexual Health and the North American Menopause Society.¹

Among the products Dr. Krychman details are neogyn^® Feminine Soothing Cream (neogyn, inc., Switzerland); RepHresh™ Vaginal Gel (Church & Dwight Co., Inc., Princeton, New Jersey); Replens™ Long-Lasting Vaginal Moisturizer (Church & Dwight); silicone- and water-based lubricants (Replens™ Silky Smooth Lubricant [Church & Dwight]; JuvaGyn^® Feminine Moisturizer [neogyn, inc.]); and ospemifene (Osphena^®, Shionogi Inc., Florham Park, New Jersey).

Dr. Krychman is interested in a new laser procedure for VVA/GSM, but comments that more study is needed before he can recommend its general use. He also talks about other exciting alternatives in the pipeline.

In an audiocast summarizing his Sunday Lunch Talk at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG) on May 3, 2015, Dr. Michael L. Krychman discusses new treatment options for vulvar and vaginal atrophy (VVA), including over-the-counter and prescription products and procedures. He emphasizes that a better understanding of the physical and anatomic changes in menopause has led to these improved options.

Dr. Krychman also recommends the use of "genitourinary syndrome of menopause" (GSM), new terminology for VVA suggested by the International Society for the Study of Women's Sexual Health and the North American Menopause Society.¹

Among the products Dr. Krychman details are neogyn^® Feminine Soothing Cream (neogyn, inc., Switzerland); RepHresh™ Vaginal Gel (Church & Dwight Co., Inc., Princeton, New Jersey); Replens™ Long-Lasting Vaginal Moisturizer (Church & Dwight); silicone- and water-based lubricants (Replens™ Silky Smooth Lubricant [Church & Dwight]; JuvaGyn^® Feminine Moisturizer [neogyn, inc.]); and ospemifene (Osphena^®, Shionogi Inc., Florham Park, New Jersey).

Dr. Krychman is interested in a new laser procedure for VVA/GSM, but comments that more study is needed before he can recommend its general use. He also talks about other exciting alternatives in the pipeline.

In an audiocast summarizing his Sunday Lunch Talk at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG) on May 3, 2015, Dr. Michael L. Krychman discusses new treatment options for vulvar and vaginal atrophy (VVA), including over-the-counter and prescription products and procedures. He emphasizes that a better understanding of the physical and anatomic changes in menopause has led to these improved options.

Dr. Krychman also recommends the use of "genitourinary syndrome of menopause" (GSM), new terminology for VVA suggested by the International Society for the Study of Women's Sexual Health and the North American Menopause Society.¹

Among the products Dr. Krychman details are neogyn^® Feminine Soothing Cream (neogyn, inc., Switzerland); RepHresh™ Vaginal Gel (Church & Dwight Co., Inc., Princeton, New Jersey); Replens™ Long-Lasting Vaginal Moisturizer (Church & Dwight); silicone- and water-based lubricants (Replens™ Silky Smooth Lubricant [Church & Dwight]; JuvaGyn^® Feminine Moisturizer [neogyn, inc.]); and ospemifene (Osphena^®, Shionogi Inc., Florham Park, New Jersey).

Dr. Krychman is interested in a new laser procedure for VVA/GSM, but comments that more study is needed before he can recommend its general use. He also talks about other exciting alternatives in the pipeline.

Transvaginal mesh not properly placed
In January 2007, polypropylene mesh (Gynecare Prolift Transvaginal Mesh; Ethicon) was inserted in a 57-year-old woman to treat bladder and rectal prolapse. The patient developed small-intestine obstruction, bladder contraction, and a large pelvic abscess. Surgical treatment of the complications included creation of a colostomy. She required daily self-catheterization. The patient died of unrelated causes after the suit was filed.

Estate’S CLAIM The gynecologist did not properly insert the mesh and did not fully inform the patient of possible complications.

PHYSICIAN’S DEFENSE The mesh was properly inserted. The patient developed an unpreventable adverse reaction to the mesh. Proper consent was obtained.

VERDICT A New York defense verdict was returned.

Polypropylene mesh removed due to pain
Polypropylene mesh (Obtryx Transobturator Midurethal Sling system, Boston Scientific Corporation [BSC]) was used to treat a woman’s stress urinary incontinence (SUI) in 2008. Following surgery, the patient reported pain. The mesh was partially removed in 2011. The patient has continuing pain and complications caused by remaining pieces of the mesh that the surgeon believes cannot be removed safely.

PATIENT’S CLAIM Although BSC warned that the material could oxidize and become brittle, the surgeon used it anyway. The mesh eroded through the urethra, causing permanent damage. BSC was negligent in the design, marketing, and instructions for Obtryx.

DEFENDANTS’ DEFENSE The surgeon  read the instructions and felt the product was safe. BSC claimed the mesh is safe for SUI use. Directions for use clearly warn of possible erosion. A BSC engineer admitted that the tissue that surrounds the mesh can shrink, encapsulating nerves and causing chronic pain.

VERDICT A Massachusetts defense verdict was returned.

Abscesses, nerve damage: $73M
A 42-year-old woman reported SUI to her gynecologist. In January 2011, the gynecologist placed polypropylene pelvic mesh (Obtryx Trans-obturator Midurethal Sling system, BSC). Following surgery, the patient reported pain and fever; pelvic abscesses were found.

Multiple procedures partially removed the mesh and treated the infection. During one procedure, her femoral and obturator nerves were damaged; she walks with a limp. Dyspareunia and pain continue. Additional operations will be needed to remove more mesh and treat continuing infection.

PATIENT’S CLAIM BSC was negligent in the product’s design and marketing. Warnings for use were inadequate concerning the nature and extent of possible permanent injuries: groin and pelvic pain, dyspareunia, nerve damage, and chronic urinary tract infections. BSC withheld or concealed clinical trial information and did not perform and report proper post-market surveillance.

When pivotal study results were published in 2009, indicating that further research was needed to confirm that Obtryx was appropriate for treating SUI, the BSC sales department received an email telling them to not share this information with physicians.

At trial, BSC corporate executives knew little about system design and warnings regarding its use. Data that BSC provided to document the safety of Obtryx were not about that product.  

MANUFACTURER’S DEFENSE Both sides agreed not to introduce discussion of the FDA and 510(k) process. BSC blamed a call-center for not passing along complaints from customers in a timely manner.

VERDICT A $73,465,000 Texas verdict was returned against BSC. The jury determined that the manufacturer displayed gross negligence; the design of the Obtryx system is faulty. The award included $50 million for exemplary damages, which the judge reduced to $11.2 million due to state caps, for a total award of $34.6 million.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Transvaginal mesh not properly placed
In January 2007, polypropylene mesh (Gynecare Prolift Transvaginal Mesh; Ethicon) was inserted in a 57-year-old woman to treat bladder and rectal prolapse. The patient developed small-intestine obstruction, bladder contraction, and a large pelvic abscess. Surgical treatment of the complications included creation of a colostomy. She required daily self-catheterization. The patient died of unrelated causes after the suit was filed.

Estate’S CLAIM The gynecologist did not properly insert the mesh and did not fully inform the patient of possible complications.

PHYSICIAN’S DEFENSE The mesh was properly inserted. The patient developed an unpreventable adverse reaction to the mesh. Proper consent was obtained.

VERDICT A New York defense verdict was returned.

Polypropylene mesh removed due to pain
Polypropylene mesh (Obtryx Transobturator Midurethal Sling system, Boston Scientific Corporation [BSC]) was used to treat a woman’s stress urinary incontinence (SUI) in 2008. Following surgery, the patient reported pain. The mesh was partially removed in 2011. The patient has continuing pain and complications caused by remaining pieces of the mesh that the surgeon believes cannot be removed safely.

PATIENT’S CLAIM Although BSC warned that the material could oxidize and become brittle, the surgeon used it anyway. The mesh eroded through the urethra, causing permanent damage. BSC was negligent in the design, marketing, and instructions for Obtryx.

DEFENDANTS’ DEFENSE The surgeon  read the instructions and felt the product was safe. BSC claimed the mesh is safe for SUI use. Directions for use clearly warn of possible erosion. A BSC engineer admitted that the tissue that surrounds the mesh can shrink, encapsulating nerves and causing chronic pain.

VERDICT A Massachusetts defense verdict was returned.

Abscesses, nerve damage: $73M
A 42-year-old woman reported SUI to her gynecologist. In January 2011, the gynecologist placed polypropylene pelvic mesh (Obtryx Trans-obturator Midurethal Sling system, BSC). Following surgery, the patient reported pain and fever; pelvic abscesses were found.

Multiple procedures partially removed the mesh and treated the infection. During one procedure, her femoral and obturator nerves were damaged; she walks with a limp. Dyspareunia and pain continue. Additional operations will be needed to remove more mesh and treat continuing infection.

PATIENT’S CLAIM BSC was negligent in the product’s design and marketing. Warnings for use were inadequate concerning the nature and extent of possible permanent injuries: groin and pelvic pain, dyspareunia, nerve damage, and chronic urinary tract infections. BSC withheld or concealed clinical trial information and did not perform and report proper post-market surveillance.

When pivotal study results were published in 2009, indicating that further research was needed to confirm that Obtryx was appropriate for treating SUI, the BSC sales department received an email telling them to not share this information with physicians.

At trial, BSC corporate executives knew little about system design and warnings regarding its use. Data that BSC provided to document the safety of Obtryx were not about that product.  

MANUFACTURER’S DEFENSE Both sides agreed not to introduce discussion of the FDA and 510(k) process. BSC blamed a call-center for not passing along complaints from customers in a timely manner.

VERDICT A $73,465,000 Texas verdict was returned against BSC. The jury determined that the manufacturer displayed gross negligence; the design of the Obtryx system is faulty. The award included $50 million for exemplary damages, which the judge reduced to $11.2 million due to state caps, for a total award of $34.6 million.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Transvaginal mesh not properly placed
In January 2007, polypropylene mesh (Gynecare Prolift Transvaginal Mesh; Ethicon) was inserted in a 57-year-old woman to treat bladder and rectal prolapse. The patient developed small-intestine obstruction, bladder contraction, and a large pelvic abscess. Surgical treatment of the complications included creation of a colostomy. She required daily self-catheterization. The patient died of unrelated causes after the suit was filed.

Estate’S CLAIM The gynecologist did not properly insert the mesh and did not fully inform the patient of possible complications.

PHYSICIAN’S DEFENSE The mesh was properly inserted. The patient developed an unpreventable adverse reaction to the mesh. Proper consent was obtained.

VERDICT A New York defense verdict was returned.

Polypropylene mesh removed due to pain
Polypropylene mesh (Obtryx Transobturator Midurethal Sling system, Boston Scientific Corporation [BSC]) was used to treat a woman’s stress urinary incontinence (SUI) in 2008. Following surgery, the patient reported pain. The mesh was partially removed in 2011. The patient has continuing pain and complications caused by remaining pieces of the mesh that the surgeon believes cannot be removed safely.

PATIENT’S CLAIM Although BSC warned that the material could oxidize and become brittle, the surgeon used it anyway. The mesh eroded through the urethra, causing permanent damage. BSC was negligent in the design, marketing, and instructions for Obtryx.

DEFENDANTS’ DEFENSE The surgeon  read the instructions and felt the product was safe. BSC claimed the mesh is safe for SUI use. Directions for use clearly warn of possible erosion. A BSC engineer admitted that the tissue that surrounds the mesh can shrink, encapsulating nerves and causing chronic pain.

VERDICT A Massachusetts defense verdict was returned.

Abscesses, nerve damage: $73M
A 42-year-old woman reported SUI to her gynecologist. In January 2011, the gynecologist placed polypropylene pelvic mesh (Obtryx Trans-obturator Midurethal Sling system, BSC). Following surgery, the patient reported pain and fever; pelvic abscesses were found.

Multiple procedures partially removed the mesh and treated the infection. During one procedure, her femoral and obturator nerves were damaged; she walks with a limp. Dyspareunia and pain continue. Additional operations will be needed to remove more mesh and treat continuing infection.

PATIENT’S CLAIM BSC was negligent in the product’s design and marketing. Warnings for use were inadequate concerning the nature and extent of possible permanent injuries: groin and pelvic pain, dyspareunia, nerve damage, and chronic urinary tract infections. BSC withheld or concealed clinical trial information and did not perform and report proper post-market surveillance.

When pivotal study results were published in 2009, indicating that further research was needed to confirm that Obtryx was appropriate for treating SUI, the BSC sales department received an email telling them to not share this information with physicians.

At trial, BSC corporate executives knew little about system design and warnings regarding its use. Data that BSC provided to document the safety of Obtryx were not about that product.  

MANUFACTURER’S DEFENSE Both sides agreed not to introduce discussion of the FDA and 510(k) process. BSC blamed a call-center for not passing along complaints from customers in a timely manner.

VERDICT A $73,465,000 Texas verdict was returned against BSC. The jury determined that the manufacturer displayed gross negligence; the design of the Obtryx system is faulty. The award included $50 million for exemplary damages, which the judge reduced to $11.2 million due to state caps, for a total award of $34.6 million.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Constipation is estimated to affect up to 27% of the general population and is more common in women, with a 2:1 female-to-male ratio.¹ Because gynecologists are frequently the main care provider for many women, understanding the diagnosis and treatment options for constipation is important. Additionally, gynecologists must manage bowel function during the perioperative period.

The diagnosis of constipation is based on the Rome III criteria.² Besides frequency of bowel movements (BMs), these criteria include evacuation symptoms and the presence of hard stools (TABLE 1). These symptoms can result from delay in colonic transit or outlet dysfunction. Constipation may be secondary to medical illness, such as central or peripheral neurologic disease, diabetes mellitus, hypothyroidism, or medications. Evaluation begins with a careful history and vaginal and perianal/anal examination.³ Initially, a trial of fiber supplementation with or without over-the-counter (OTC) laxatives may be tried (TABLE 2). If patients have an inadequate response to this therapy, further evaluation may be pursued (ALGORITHM).

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In this article, we review the results of randomized trials comparing the efficacy of OTC medical treatments for constipation, including daily, low-dose polyethylene glycol (PEG) and probiotics. Additionally, we review key trials evaluating perioperative bowel management prior to laparoscopic gynecologic and vaginal surgery.
 

LONG-TERM PEG USAGE SAFE AND EFFECTIVE?

Corazziari E, Badiali D, Bazzocchi G, et al. Long-term efficacy, safety, and tolerability of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut. 2000;46(4):522–526.

In this multicenter, randomized, double-blind, placebo-controlled, parallel trial, investigators evaluated the safety, efficacy, and tolerability of a daily low-dose PEG-based osmotic diuretic.

Details of the study
Seventy-eight patients (80% of them female) aged 18 to 75 years with chronic constipation, defined by Rome III diagnostic criteria, underwent a 4-week “run-in” period, with a standardized daily diet of fiber 15 g, water 1500 mL, and twice-daily PMF-100 (PEG/osmotic solution). Patients were randomized if they responded to the regimen, with response defined as having at least two BMs per week and no defecatory disturbance or at least three BMs per week with or without defecatory disturbance. Eight patients were not randomized, one due to nonresponsiveness. Study patients completed 20 weeks of either twice-daily PMF-100 or placebo. Patients, at their own discretion, decreased the frequency of the study drug based on the frequency of their BMs. Use of another laxative was not allowed unless a BM had not occurred over a 5-day period.

The combined primary outcome was at least three BMs per week, no defecatory disturbances, and no additional laxative use. Secondary outcomes (frequency of BMs and defecatory disturbances) were assessed using a bowel diary.

No differences were noted in baseline measurements between the two groups. Of the PMF-100 group, 70% completed the study, compared with 30% of the placebo group (P<.01). Nonresponse to treatment was the reason for dropout in 7% and 46% of patients, respectively (P<.005). Other causes of withdrawal did not differ between the groups.

At the end of the 20 weeks, 77% of patients in the PMF-100 group reported remission, compared with 20% in the placebo group (P<.001). During the study, the PMF-100 group reported more BMs per week (7.4 vs 4.3; P<.001). Furthermore, the treatment group was less likely to report straining at defecation, hard/pellet stools, and need for use of additional laxatives. Adverse events (nausea, anal pain/itching, hematochezia, epigastric pain, and fecal incontinence) were similar between groups. There were no differences in laboratory values.

Study strengths
This was a well-designed trial showing the safety, efficacy, and tolerability of a daily low-dose PEG-based osmotic diuretic. The population was mainly women with functional chronic constipation, similar to a gynecologic population. The results of this trial are consistent with what has been shown for other trials various PEG preparations.^4,5

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Women who fail initial fiber therapy may respond to daily low-dose PEG on a continuous basis. Resolution of constipation and defecatory symptoms is likely and should be seen within 1 month. Therapy can be continued safely for at least 6 months.

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NEW AND TRENDY OTC TREATMENT OPTION

Del Piano M, Carmagnola S, Anderloni A, et al. The use of probiotics in healthy volunteers with evacuation disorders and hard stools: a double-blind, randomized, placebo-controlled study. J Clin Gastroenterol. 2010;44(suppl 1):S30–S34.

Factors such as age, unhealthy diet, and use of prescription drugs alter the intestinal bacterial flora. As patients strive for a more holistic approach to their health, interest is growing in the benefit of probiotics for treating chronic constipation. To explore the value of such probiotics, Del Piano and colleagues conducted a three-armed, randomized, double-blind placebo-controlled trial of two different probiotic preparations and a placebo among patients aged 24 to 71 years with evacuation disorders and constipation.

Details of the study
One probiotic preparation (A) was composed of Lactobacillus plantarum and Bifidobacterium breve at a concentration of 2.5×109 cfu per day; the other (B) was composed of Bifidobacterium animalis subspecies lactis at a concentration of 5×10⁹ cfu per day. Patients took their preparation for 30 days and recorded data on weekly defecations (primary outcome), along with feces consistency, ease of expulsion, sensation emptying, anal itching/burning/pain with defecation, and abdominal bloating (secondary outcomes).

A total of 300 patients were enrolled in the study; 50% were female. No difference was noted in baseline symptoms among the three groups. No change from baseline was noted in BMs per week within the placebo group during the 30 days (5.6 vs 5.8, respectively). However, both probiotic preparations resulted in increased bowel frequency by day 30 (5.3 vs 7.3 BMs per week for probiotic A [P<.001] and 5.8 vs 6.9 BMs per week for probiotic B [P<.001]).

When comparing each probiotic with the placebo at days 15 and 30, a statistically significant increase in bowel frequency was found with each probiotic preparation. Furthermore, all secondary outcomes improved during the 30 days with the probiotic preparations but not the placebo. There was a statistically significant improvement in these variables when either probiotic was compared with placebo. No adverse events were reported.

Strengths and limitations
This randomized, double-blind, placebo-controlled trial showed improvement in bowel frequency, based on a bowel diary, with two different probiotic preparations when compared with placebo. The study population did not have to meet Rome III criteria for constipation, and baseline frequency of BMs was high. Patients did report subjective improvement in their defecatory symptoms with both probiotic preparations, but use of validated questionnaires would have strengthened this finding.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Patients with mild constipation and defecatory complaints may benefit from the addition of a probiotic preparation. However, more thorough studies need to be performed to characterize the true extent of probiotics’ benefits.

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BOWEL PREP BEFORE LAPAROSCOPIC GYNECOLOGIC SURGERY

Siedhoff MT, Clark LH, Hobbs KA, Findley AD, Moulder JK, Garrett JM. Mechanic bowel preparation before laparoscopic hysterectomy: a randomized controlled trial. Obstet Gynecol. 2014;123(3):562–567.

Over the past decade, extrapolation of data from colorectal surgery literature, showing no benefit from preoperative mechanical bowel preparation,⁶ has led to less frequent use of mechanical bowel preparations for open benign gynecologic surgery. Nevertheless, there has been slower adoption of this practice with laparoscopic and vaginal surgery. In a recent study, Siedhoff and colleagues explored surgeons’ assessments of surgical field exposure in patients who did and did not complete preoperative mechanical bowel preparation.

Details of the study
This was a single-masked, randomized, controlled trial involving women undergoing laparoscopic hysterectomy for benign indications. Patients were randomly assigned to either a sodium phosphate enema the night before surgery and, if their stool was not clear, another enema on the morning of surgery versus no preparation. All patients had clear liquids the day prior to surgery, then fasted beginning at midnight. The surgeon was blinded to the randomization.

The primary outcome was a questionnaire completed by the surgeon that assessed surgical field exposure. Secondarily, patients completed a questionnaire addressing symptoms (cramps, hunger, bloating, embarrassment, insomnia, weakness, dizziness, thirst, nausea, and incontinence).

Baseline characteristics of the 160 randomized patients did not differ between the two groups. Analysis was on an intent-to-treat basis, but only two patients did not complete the bowel preparation. Overall, the study population had a mean age of 41 and body mass index of 33.5 kg/m². No differences were noted in surgical characteristics between the two groups, including complication rate. The mean surgery time was 139 minutes with a mean estimated blood loss of 61 mL and a mean uterine weight of 385 g.

The surgeon’s assessment of the surgical field did not differ between the two groups. This finding also held true when subgroup analysis was performed for obesity, endometriosis, irritable bowel syndrome or inflammatory bowel disease, and chronic constipation. Interestingly, the odds of the surgeon guessing whether a patient had had a preparation were 50:50. The only difference in patient symptoms was an increase in insomnia in the no-preparation group.

Minor drawback
This well-performed trial demonstrated no significant value for mechanical bowel preparation before benign laparoscopic hysterectomy in a young population. How these results might extrapolate to an older population who may have a higher rate of prior pelvic surgery or diverticular disease is uncertain.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Women undergoing laparoscopic hysterectomy for a benign indication may forego a mechanical bowel preparation as such preparation did not improve the surgical field.

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BOWEL PREP BEFORE VAGINAL SURGERY

Ballard AC, Parker-Autry CY, Markland AD, Varner RE, Huisingh C, Richter HE. Bowel preparation before vaginal prolapse surgery: a randomized controlled trial. Obstet Gynecol. 2014;123(2 pt 1):232–238.

In this single-masked, randomized controlled trial in women undergoing reconstructive vaginal prolapse surgery, Ballard and colleagues randomly assigned patients to either a clear liquid diet with two saline enemas the day before surgery or a regular diet the day before surgery.

Details of the study
All 150 patients were instructed to fast beginning at midnight the night before surgery, and the surgeon was blinded to randomization. The study’s primary outcome was the surgeon’s perception of the operative field assessed by a questionnaire. The secondary outcome was the patient’s satisfaction with their preoperative regimen as reported on validated questionnaires.

An intent-to-treat analysis was performed (mean age, 60 years); 84% of patients assigned to bowel preparation completed more than 50% of the enemas. Baseline characteristics and surgical procedures were similar between groups. Approximately 33% of patients underwent hysterectomy concomitantly with the prolapse repair. Operative time, estimated blood loss, and bowel injury were similar between the two groups.

No difference between groups was noted in the surgeons’ assessment of the surgical field—which was rated as excellent or good in 85% of patients who underwent the bowel preparation compared with 90% in the no-preparation group (P = .3). Additionally, no difference was noted in the presence of rectal stool or gas by inspection and palpation. Patient satisfaction was significantly lower among those who underwent bowel preparation compared with patients who did not. Patients undergoing bowel preparation were more likely to have abdominal fullness or bloating (P = .004), abdominal cramps or pain (P<.001), anal irritation (P<.001), and hunger pains (P<.001).

Prep group saw no benefit and decreased satisfaction
This well-performed clinical trial showed that the use of mechanical bowel preparation did not significantly improve surgeons’ intraoperative acceptability of the operative field during vaginal prolapse surgery. However, approximately 25% of patients underwent sacrospinous suspensions; therefore, intraperitoneal access was not necessary in these patients. The study results demonstrated decreased patient satisfaction and more distressing bowel symptoms in patients who underwent a mechanical bowel preparation with an enema.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Use of a mechanical bowel preparation is not necessary to improve the surgical field in vaginal prolapse surgery. Not having patients undergo a bowel preparation will improve patients’ assessment of their preparation for surgery.

--------------

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Constipation is estimated to affect up to 27% of the general population and is more common in women, with a 2:1 female-to-male ratio.¹ Because gynecologists are frequently the main care provider for many women, understanding the diagnosis and treatment options for constipation is important. Additionally, gynecologists must manage bowel function during the perioperative period.

The diagnosis of constipation is based on the Rome III criteria.² Besides frequency of bowel movements (BMs), these criteria include evacuation symptoms and the presence of hard stools (TABLE 1). These symptoms can result from delay in colonic transit or outlet dysfunction. Constipation may be secondary to medical illness, such as central or peripheral neurologic disease, diabetes mellitus, hypothyroidism, or medications. Evaluation begins with a careful history and vaginal and perianal/anal examination.³ Initially, a trial of fiber supplementation with or without over-the-counter (OTC) laxatives may be tried (TABLE 2). If patients have an inadequate response to this therapy, further evaluation may be pursued (ALGORITHM).

------

--------

In this article, we review the results of randomized trials comparing the efficacy of OTC medical treatments for constipation, including daily, low-dose polyethylene glycol (PEG) and probiotics. Additionally, we review key trials evaluating perioperative bowel management prior to laparoscopic gynecologic and vaginal surgery.
 

LONG-TERM PEG USAGE SAFE AND EFFECTIVE?

Corazziari E, Badiali D, Bazzocchi G, et al. Long-term efficacy, safety, and tolerability of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut. 2000;46(4):522–526.

In this multicenter, randomized, double-blind, placebo-controlled, parallel trial, investigators evaluated the safety, efficacy, and tolerability of a daily low-dose PEG-based osmotic diuretic.

Details of the study
Seventy-eight patients (80% of them female) aged 18 to 75 years with chronic constipation, defined by Rome III diagnostic criteria, underwent a 4-week “run-in” period, with a standardized daily diet of fiber 15 g, water 1500 mL, and twice-daily PMF-100 (PEG/osmotic solution). Patients were randomized if they responded to the regimen, with response defined as having at least two BMs per week and no defecatory disturbance or at least three BMs per week with or without defecatory disturbance. Eight patients were not randomized, one due to nonresponsiveness. Study patients completed 20 weeks of either twice-daily PMF-100 or placebo. Patients, at their own discretion, decreased the frequency of the study drug based on the frequency of their BMs. Use of another laxative was not allowed unless a BM had not occurred over a 5-day period.

The combined primary outcome was at least three BMs per week, no defecatory disturbances, and no additional laxative use. Secondary outcomes (frequency of BMs and defecatory disturbances) were assessed using a bowel diary.

No differences were noted in baseline measurements between the two groups. Of the PMF-100 group, 70% completed the study, compared with 30% of the placebo group (P<.01). Nonresponse to treatment was the reason for dropout in 7% and 46% of patients, respectively (P<.005). Other causes of withdrawal did not differ between the groups.

At the end of the 20 weeks, 77% of patients in the PMF-100 group reported remission, compared with 20% in the placebo group (P<.001). During the study, the PMF-100 group reported more BMs per week (7.4 vs 4.3; P<.001). Furthermore, the treatment group was less likely to report straining at defecation, hard/pellet stools, and need for use of additional laxatives. Adverse events (nausea, anal pain/itching, hematochezia, epigastric pain, and fecal incontinence) were similar between groups. There were no differences in laboratory values.

Study strengths
This was a well-designed trial showing the safety, efficacy, and tolerability of a daily low-dose PEG-based osmotic diuretic. The population was mainly women with functional chronic constipation, similar to a gynecologic population. The results of this trial are consistent with what has been shown for other trials various PEG preparations.^4,5

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Women who fail initial fiber therapy may respond to daily low-dose PEG on a continuous basis. Resolution of constipation and defecatory symptoms is likely and should be seen within 1 month. Therapy can be continued safely for at least 6 months.

--------------

NEW AND TRENDY OTC TREATMENT OPTION

Del Piano M, Carmagnola S, Anderloni A, et al. The use of probiotics in healthy volunteers with evacuation disorders and hard stools: a double-blind, randomized, placebo-controlled study. J Clin Gastroenterol. 2010;44(suppl 1):S30–S34.

Factors such as age, unhealthy diet, and use of prescription drugs alter the intestinal bacterial flora. As patients strive for a more holistic approach to their health, interest is growing in the benefit of probiotics for treating chronic constipation. To explore the value of such probiotics, Del Piano and colleagues conducted a three-armed, randomized, double-blind placebo-controlled trial of two different probiotic preparations and a placebo among patients aged 24 to 71 years with evacuation disorders and constipation.

Details of the study
One probiotic preparation (A) was composed of Lactobacillus plantarum and Bifidobacterium breve at a concentration of 2.5×109 cfu per day; the other (B) was composed of Bifidobacterium animalis subspecies lactis at a concentration of 5×10⁹ cfu per day. Patients took their preparation for 30 days and recorded data on weekly defecations (primary outcome), along with feces consistency, ease of expulsion, sensation emptying, anal itching/burning/pain with defecation, and abdominal bloating (secondary outcomes).

A total of 300 patients were enrolled in the study; 50% were female. No difference was noted in baseline symptoms among the three groups. No change from baseline was noted in BMs per week within the placebo group during the 30 days (5.6 vs 5.8, respectively). However, both probiotic preparations resulted in increased bowel frequency by day 30 (5.3 vs 7.3 BMs per week for probiotic A [P<.001] and 5.8 vs 6.9 BMs per week for probiotic B [P<.001]).

When comparing each probiotic with the placebo at days 15 and 30, a statistically significant increase in bowel frequency was found with each probiotic preparation. Furthermore, all secondary outcomes improved during the 30 days with the probiotic preparations but not the placebo. There was a statistically significant improvement in these variables when either probiotic was compared with placebo. No adverse events were reported.

Strengths and limitations
This randomized, double-blind, placebo-controlled trial showed improvement in bowel frequency, based on a bowel diary, with two different probiotic preparations when compared with placebo. The study population did not have to meet Rome III criteria for constipation, and baseline frequency of BMs was high. Patients did report subjective improvement in their defecatory symptoms with both probiotic preparations, but use of validated questionnaires would have strengthened this finding.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Patients with mild constipation and defecatory complaints may benefit from the addition of a probiotic preparation. However, more thorough studies need to be performed to characterize the true extent of probiotics’ benefits.

--------------

BOWEL PREP BEFORE LAPAROSCOPIC GYNECOLOGIC SURGERY

Siedhoff MT, Clark LH, Hobbs KA, Findley AD, Moulder JK, Garrett JM. Mechanic bowel preparation before laparoscopic hysterectomy: a randomized controlled trial. Obstet Gynecol. 2014;123(3):562–567.

Over the past decade, extrapolation of data from colorectal surgery literature, showing no benefit from preoperative mechanical bowel preparation,⁶ has led to less frequent use of mechanical bowel preparations for open benign gynecologic surgery. Nevertheless, there has been slower adoption of this practice with laparoscopic and vaginal surgery. In a recent study, Siedhoff and colleagues explored surgeons’ assessments of surgical field exposure in patients who did and did not complete preoperative mechanical bowel preparation.

Details of the study
This was a single-masked, randomized, controlled trial involving women undergoing laparoscopic hysterectomy for benign indications. Patients were randomly assigned to either a sodium phosphate enema the night before surgery and, if their stool was not clear, another enema on the morning of surgery versus no preparation. All patients had clear liquids the day prior to surgery, then fasted beginning at midnight. The surgeon was blinded to the randomization.

The primary outcome was a questionnaire completed by the surgeon that assessed surgical field exposure. Secondarily, patients completed a questionnaire addressing symptoms (cramps, hunger, bloating, embarrassment, insomnia, weakness, dizziness, thirst, nausea, and incontinence).

Baseline characteristics of the 160 randomized patients did not differ between the two groups. Analysis was on an intent-to-treat basis, but only two patients did not complete the bowel preparation. Overall, the study population had a mean age of 41 and body mass index of 33.5 kg/m². No differences were noted in surgical characteristics between the two groups, including complication rate. The mean surgery time was 139 minutes with a mean estimated blood loss of 61 mL and a mean uterine weight of 385 g.

The surgeon’s assessment of the surgical field did not differ between the two groups. This finding also held true when subgroup analysis was performed for obesity, endometriosis, irritable bowel syndrome or inflammatory bowel disease, and chronic constipation. Interestingly, the odds of the surgeon guessing whether a patient had had a preparation were 50:50. The only difference in patient symptoms was an increase in insomnia in the no-preparation group.

Minor drawback
This well-performed trial demonstrated no significant value for mechanical bowel preparation before benign laparoscopic hysterectomy in a young population. How these results might extrapolate to an older population who may have a higher rate of prior pelvic surgery or diverticular disease is uncertain.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Women undergoing laparoscopic hysterectomy for a benign indication may forego a mechanical bowel preparation as such preparation did not improve the surgical field.

--------------

BOWEL PREP BEFORE VAGINAL SURGERY

Ballard AC, Parker-Autry CY, Markland AD, Varner RE, Huisingh C, Richter HE. Bowel preparation before vaginal prolapse surgery: a randomized controlled trial. Obstet Gynecol. 2014;123(2 pt 1):232–238.

In this single-masked, randomized controlled trial in women undergoing reconstructive vaginal prolapse surgery, Ballard and colleagues randomly assigned patients to either a clear liquid diet with two saline enemas the day before surgery or a regular diet the day before surgery.

Details of the study
All 150 patients were instructed to fast beginning at midnight the night before surgery, and the surgeon was blinded to randomization. The study’s primary outcome was the surgeon’s perception of the operative field assessed by a questionnaire. The secondary outcome was the patient’s satisfaction with their preoperative regimen as reported on validated questionnaires.

An intent-to-treat analysis was performed (mean age, 60 years); 84% of patients assigned to bowel preparation completed more than 50% of the enemas. Baseline characteristics and surgical procedures were similar between groups. Approximately 33% of patients underwent hysterectomy concomitantly with the prolapse repair. Operative time, estimated blood loss, and bowel injury were similar between the two groups.

No difference between groups was noted in the surgeons’ assessment of the surgical field—which was rated as excellent or good in 85% of patients who underwent the bowel preparation compared with 90% in the no-preparation group (P = .3). Additionally, no difference was noted in the presence of rectal stool or gas by inspection and palpation. Patient satisfaction was significantly lower among those who underwent bowel preparation compared with patients who did not. Patients undergoing bowel preparation were more likely to have abdominal fullness or bloating (P = .004), abdominal cramps or pain (P<.001), anal irritation (P<.001), and hunger pains (P<.001).

Prep group saw no benefit and decreased satisfaction
This well-performed clinical trial showed that the use of mechanical bowel preparation did not significantly improve surgeons’ intraoperative acceptability of the operative field during vaginal prolapse surgery. However, approximately 25% of patients underwent sacrospinous suspensions; therefore, intraperitoneal access was not necessary in these patients. The study results demonstrated decreased patient satisfaction and more distressing bowel symptoms in patients who underwent a mechanical bowel preparation with an enema.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Use of a mechanical bowel preparation is not necessary to improve the surgical field in vaginal prolapse surgery. Not having patients undergo a bowel preparation will improve patients’ assessment of their preparation for surgery.

--------------

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Constipation is estimated to affect up to 27% of the general population and is more common in women, with a 2:1 female-to-male ratio.¹ Because gynecologists are frequently the main care provider for many women, understanding the diagnosis and treatment options for constipation is important. Additionally, gynecologists must manage bowel function during the perioperative period.

The diagnosis of constipation is based on the Rome III criteria.² Besides frequency of bowel movements (BMs), these criteria include evacuation symptoms and the presence of hard stools (TABLE 1). These symptoms can result from delay in colonic transit or outlet dysfunction. Constipation may be secondary to medical illness, such as central or peripheral neurologic disease, diabetes mellitus, hypothyroidism, or medications. Evaluation begins with a careful history and vaginal and perianal/anal examination.³ Initially, a trial of fiber supplementation with or without over-the-counter (OTC) laxatives may be tried (TABLE 2). If patients have an inadequate response to this therapy, further evaluation may be pursued (ALGORITHM).

------

--------

In this article, we review the results of randomized trials comparing the efficacy of OTC medical treatments for constipation, including daily, low-dose polyethylene glycol (PEG) and probiotics. Additionally, we review key trials evaluating perioperative bowel management prior to laparoscopic gynecologic and vaginal surgery.
 

LONG-TERM PEG USAGE SAFE AND EFFECTIVE?

Corazziari E, Badiali D, Bazzocchi G, et al. Long-term efficacy, safety, and tolerability of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut. 2000;46(4):522–526.

In this multicenter, randomized, double-blind, placebo-controlled, parallel trial, investigators evaluated the safety, efficacy, and tolerability of a daily low-dose PEG-based osmotic diuretic.

Details of the study
Seventy-eight patients (80% of them female) aged 18 to 75 years with chronic constipation, defined by Rome III diagnostic criteria, underwent a 4-week “run-in” period, with a standardized daily diet of fiber 15 g, water 1500 mL, and twice-daily PMF-100 (PEG/osmotic solution). Patients were randomized if they responded to the regimen, with response defined as having at least two BMs per week and no defecatory disturbance or at least three BMs per week with or without defecatory disturbance. Eight patients were not randomized, one due to nonresponsiveness. Study patients completed 20 weeks of either twice-daily PMF-100 or placebo. Patients, at their own discretion, decreased the frequency of the study drug based on the frequency of their BMs. Use of another laxative was not allowed unless a BM had not occurred over a 5-day period.

The combined primary outcome was at least three BMs per week, no defecatory disturbances, and no additional laxative use. Secondary outcomes (frequency of BMs and defecatory disturbances) were assessed using a bowel diary.

No differences were noted in baseline measurements between the two groups. Of the PMF-100 group, 70% completed the study, compared with 30% of the placebo group (P<.01). Nonresponse to treatment was the reason for dropout in 7% and 46% of patients, respectively (P<.005). Other causes of withdrawal did not differ between the groups.

At the end of the 20 weeks, 77% of patients in the PMF-100 group reported remission, compared with 20% in the placebo group (P<.001). During the study, the PMF-100 group reported more BMs per week (7.4 vs 4.3; P<.001). Furthermore, the treatment group was less likely to report straining at defecation, hard/pellet stools, and need for use of additional laxatives. Adverse events (nausea, anal pain/itching, hematochezia, epigastric pain, and fecal incontinence) were similar between groups. There were no differences in laboratory values.

Study strengths
This was a well-designed trial showing the safety, efficacy, and tolerability of a daily low-dose PEG-based osmotic diuretic. The population was mainly women with functional chronic constipation, similar to a gynecologic population. The results of this trial are consistent with what has been shown for other trials various PEG preparations.^4,5

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Women who fail initial fiber therapy may respond to daily low-dose PEG on a continuous basis. Resolution of constipation and defecatory symptoms is likely and should be seen within 1 month. Therapy can be continued safely for at least 6 months.

--------------

NEW AND TRENDY OTC TREATMENT OPTION

Del Piano M, Carmagnola S, Anderloni A, et al. The use of probiotics in healthy volunteers with evacuation disorders and hard stools: a double-blind, randomized, placebo-controlled study. J Clin Gastroenterol. 2010;44(suppl 1):S30–S34.

Factors such as age, unhealthy diet, and use of prescription drugs alter the intestinal bacterial flora. As patients strive for a more holistic approach to their health, interest is growing in the benefit of probiotics for treating chronic constipation. To explore the value of such probiotics, Del Piano and colleagues conducted a three-armed, randomized, double-blind placebo-controlled trial of two different probiotic preparations and a placebo among patients aged 24 to 71 years with evacuation disorders and constipation.

Details of the study
One probiotic preparation (A) was composed of Lactobacillus plantarum and Bifidobacterium breve at a concentration of 2.5×109 cfu per day; the other (B) was composed of Bifidobacterium animalis subspecies lactis at a concentration of 5×10⁹ cfu per day. Patients took their preparation for 30 days and recorded data on weekly defecations (primary outcome), along with feces consistency, ease of expulsion, sensation emptying, anal itching/burning/pain with defecation, and abdominal bloating (secondary outcomes).

A total of 300 patients were enrolled in the study; 50% were female. No difference was noted in baseline symptoms among the three groups. No change from baseline was noted in BMs per week within the placebo group during the 30 days (5.6 vs 5.8, respectively). However, both probiotic preparations resulted in increased bowel frequency by day 30 (5.3 vs 7.3 BMs per week for probiotic A [P<.001] and 5.8 vs 6.9 BMs per week for probiotic B [P<.001]).

When comparing each probiotic with the placebo at days 15 and 30, a statistically significant increase in bowel frequency was found with each probiotic preparation. Furthermore, all secondary outcomes improved during the 30 days with the probiotic preparations but not the placebo. There was a statistically significant improvement in these variables when either probiotic was compared with placebo. No adverse events were reported.

Strengths and limitations
This randomized, double-blind, placebo-controlled trial showed improvement in bowel frequency, based on a bowel diary, with two different probiotic preparations when compared with placebo. The study population did not have to meet Rome III criteria for constipation, and baseline frequency of BMs was high. Patients did report subjective improvement in their defecatory symptoms with both probiotic preparations, but use of validated questionnaires would have strengthened this finding.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Patients with mild constipation and defecatory complaints may benefit from the addition of a probiotic preparation. However, more thorough studies need to be performed to characterize the true extent of probiotics’ benefits.

--------------

BOWEL PREP BEFORE LAPAROSCOPIC GYNECOLOGIC SURGERY

Siedhoff MT, Clark LH, Hobbs KA, Findley AD, Moulder JK, Garrett JM. Mechanic bowel preparation before laparoscopic hysterectomy: a randomized controlled trial. Obstet Gynecol. 2014;123(3):562–567.

Over the past decade, extrapolation of data from colorectal surgery literature, showing no benefit from preoperative mechanical bowel preparation,⁶ has led to less frequent use of mechanical bowel preparations for open benign gynecologic surgery. Nevertheless, there has been slower adoption of this practice with laparoscopic and vaginal surgery. In a recent study, Siedhoff and colleagues explored surgeons’ assessments of surgical field exposure in patients who did and did not complete preoperative mechanical bowel preparation.

Details of the study
This was a single-masked, randomized, controlled trial involving women undergoing laparoscopic hysterectomy for benign indications. Patients were randomly assigned to either a sodium phosphate enema the night before surgery and, if their stool was not clear, another enema on the morning of surgery versus no preparation. All patients had clear liquids the day prior to surgery, then fasted beginning at midnight. The surgeon was blinded to the randomization.

The primary outcome was a questionnaire completed by the surgeon that assessed surgical field exposure. Secondarily, patients completed a questionnaire addressing symptoms (cramps, hunger, bloating, embarrassment, insomnia, weakness, dizziness, thirst, nausea, and incontinence).

Baseline characteristics of the 160 randomized patients did not differ between the two groups. Analysis was on an intent-to-treat basis, but only two patients did not complete the bowel preparation. Overall, the study population had a mean age of 41 and body mass index of 33.5 kg/m². No differences were noted in surgical characteristics between the two groups, including complication rate. The mean surgery time was 139 minutes with a mean estimated blood loss of 61 mL and a mean uterine weight of 385 g.

The surgeon’s assessment of the surgical field did not differ between the two groups. This finding also held true when subgroup analysis was performed for obesity, endometriosis, irritable bowel syndrome or inflammatory bowel disease, and chronic constipation. Interestingly, the odds of the surgeon guessing whether a patient had had a preparation were 50:50. The only difference in patient symptoms was an increase in insomnia in the no-preparation group.

Minor drawback
This well-performed trial demonstrated no significant value for mechanical bowel preparation before benign laparoscopic hysterectomy in a young population. How these results might extrapolate to an older population who may have a higher rate of prior pelvic surgery or diverticular disease is uncertain.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Women undergoing laparoscopic hysterectomy for a benign indication may forego a mechanical bowel preparation as such preparation did not improve the surgical field.

--------------

BOWEL PREP BEFORE VAGINAL SURGERY

Ballard AC, Parker-Autry CY, Markland AD, Varner RE, Huisingh C, Richter HE. Bowel preparation before vaginal prolapse surgery: a randomized controlled trial. Obstet Gynecol. 2014;123(2 pt 1):232–238.

In this single-masked, randomized controlled trial in women undergoing reconstructive vaginal prolapse surgery, Ballard and colleagues randomly assigned patients to either a clear liquid diet with two saline enemas the day before surgery or a regular diet the day before surgery.

Details of the study
All 150 patients were instructed to fast beginning at midnight the night before surgery, and the surgeon was blinded to randomization. The study’s primary outcome was the surgeon’s perception of the operative field assessed by a questionnaire. The secondary outcome was the patient’s satisfaction with their preoperative regimen as reported on validated questionnaires.

An intent-to-treat analysis was performed (mean age, 60 years); 84% of patients assigned to bowel preparation completed more than 50% of the enemas. Baseline characteristics and surgical procedures were similar between groups. Approximately 33% of patients underwent hysterectomy concomitantly with the prolapse repair. Operative time, estimated blood loss, and bowel injury were similar between the two groups.

No difference between groups was noted in the surgeons’ assessment of the surgical field—which was rated as excellent or good in 85% of patients who underwent the bowel preparation compared with 90% in the no-preparation group (P = .3). Additionally, no difference was noted in the presence of rectal stool or gas by inspection and palpation. Patient satisfaction was significantly lower among those who underwent bowel preparation compared with patients who did not. Patients undergoing bowel preparation were more likely to have abdominal fullness or bloating (P = .004), abdominal cramps or pain (P<.001), anal irritation (P<.001), and hunger pains (P<.001).

Prep group saw no benefit and decreased satisfaction
This well-performed clinical trial showed that the use of mechanical bowel preparation did not significantly improve surgeons’ intraoperative acceptability of the operative field during vaginal prolapse surgery. However, approximately 25% of patients underwent sacrospinous suspensions; therefore, intraperitoneal access was not necessary in these patients. The study results demonstrated decreased patient satisfaction and more distressing bowel symptoms in patients who underwent a mechanical bowel preparation with an enema.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Use of a mechanical bowel preparation is not necessary to improve the surgical field in vaginal prolapse surgery. Not having patients undergo a bowel preparation will improve patients’ assessment of their preparation for surgery.

--------------

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Suddenly, indigo carmine is in short supply throughout the United States. One manufacturer has stopped production because of a raw materials shortage; another is experiencing manufacturing delays. Neither company can estimate a resupply or product return date.¹

Indigo carmine is approved by the US Food and Drug Administration (FDA) to localize ureteral orifices during cystoscopy and is commonly used in obstetrics and gynecology as a marker dye in the following additional situations:

• administered in a dilute solution via a catheter to back fill the bladder and test for bladder injury
• administered via a cannula in the uterine cavity to test the patency of the fallopian tubes
• injected into the amniotic fluid compartment to test for premature rupture of the membranes (PROM)
• injected into the amniotic fluid of a twin gestation to mark the amniotic fluid of one twin.

With this agent in short supply, we need to identify alternative marker dyes to use in our clinical practice. In this editorial, I provide a list of possible options to replace indigo carmine. Evidence supporting the use and safety of marker dyes in obstetrics and gynecology is based on small cohorts or case reports. The available evidence is of modest to low quality, and it is especially challenging to identify uncommon adverse effects. Consequently, expert opinion guides most practice recommendations.

Options to test the function of the ureters at cystoscopy
Given the lack of availability of indigo carmine, I recommend one of the following three options to test the function of the ureters at cystoscopy.

Partially fill the bladder with a solution of either sterile water or a 10% dextrose solution. (Experienced surgeons may prefer to use saline.) The turbulence of the interaction between the ureteral urine jet and instilled fluid in the bladder may permit visualization of the urine stream exiting the ureteral orifices as it swirls through the sterile water or dextrose solution. Both sterile water and a 10% dextrose solution offer a contrast in viscosity between the urine and the cystoscopy fluid, which may enhance the ability to detect the urine jet leaving the ureter.²

Administer IV methylene blue. Methylene blue is FDA approved for methemoglobinemia treatment. For this indication, it is administered intravenously at a dose of 1 to 2 mg/kgover 5 to 10 minutes. Paradoxically, when administered at a dose of >7 mg/kg, methylene blue can cause methemoglobinemia.³

Methylene blue often is provided as a 1% solution of 10 mg/mL in 10-mL vials. To use intravenous (IV) methylene blue to test ureteral function at cystoscopy, administer IV methylene blue 50 mg over 5 minutes. Use the cystoscope to view the colored urine exiting the ureteral orifices.^4,5 Administering a small dose of IV furosemide may accelerate the appearance of methylene blue in the urine.

When to use caution. Methylene blue blocks serotonin metabolism by inhibiting monoamine oxidase and may precipitate a serotonin syndrome in patients taking selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs).

Common findings in the serotonin syndrome include: temperature above 38° C (100.4° F), anxiety, agitation, delirium, clonus, tremor, and hypertonia.⁶ I recommend that you DO NOT use IV methylene blue in patients taking these medications.^7,8

Great caution should be used before administering IV methylene blue in the presence of the following clinical situations:

• renal impairment  
• G6PD deficiency
• pediatric patients.

Methylene blue never should be given by a subcutaneous or intrathecal route. In pregnant women it should never be injected into the amniotic fluid compartment.

Use preoperative oral phenazo-pyridine. If the preoperative plan includes a cystoscopy procedure to test ureteral function, administering oral phenazopyridine in the preoperative holding area will result in colorization of the urine within 30 minutes, and it will persist for approximately 4 to 5 hours. To use this approach, administer one dose of phenazopyridine (Pyridium, Azo-Gesic), 100 mg or 200 mg orally, 30 minutes to 1 hour before the planned surgical start time, in the preoperative holding area.⁹ During cystoscopy, the urine from the ureteral jet will be colored orange.

When to use caution. Phenazo­pyridine should not be administered to patients with G6PD deficiency.

Option to test for bladder injury
Methylene blue. If methylene blue is used to test the integrity of the bladder, I recommend diluting 10 mg methylene blue in 1 L normal saline and then instilling the dilute solution through a catheter into the bladder.¹⁰

It is unlikely that this technique will be associated with sufficient methylene blue absorption to cause a serotonin syndrome. Therefore, this technique can be used in patients taking SSRIs, SNRIs, and MAOIs.

Option to test patency of the fallopian tubes (chromopertubation)
Methylene blue. If methylene blue is used via a cannula in the uterine cavity to test the patency of the fallopian tubes, I recommend diluting 10 mg methylene blue in 150 mL normal saline and using the dilute solution to test tubal patency.

It is unlikely that this process will lead to sufficient methylene blue absorption to cause a serotonin syndrome. Therefore, this technique can be used in patients taking SSRIs, SNRIs and MAOIs. However, if intrauterine injection of the dilute dye solution results in extravasation of the dye into the pelvic veins, a significant amount of dye can enter the circulation.¹¹ There are case reports of anaphylaxis following intrauterine injection of methylene blue to test tubal patency.^12,13

Options to diagnose PROM and to use for twin amniocentesis
None. Most experts recommend against the intra-amniotic injection of methylene blue to diagnose PROM or in twin amniocentesis procedures. Methylene blue injected into the intra-amniotic fluid during amniocentesis in multiple gestations has been reported to cause fetal bowel obstruction or atresia.^14,15 Fetal death also has been reported.¹⁶ Decades ago, indocyanine green, which is FDA approved to determine cardiac output, liver blood flow, and hepatic function, was reported to be useful to mark one sac of a twin gestation during amniocentesis.¹⁷ With modern ultrasonography technology, the need to rely on a dye to mark a sac of a twin has decreased significantly.

Our only option is to cope—effectively as possible Over decades, the medical community develops patterns of patient care that are critically dependent on the availability of key pharmaceuticals and devices. When a pharmaceutical or device suddenly becomes unavailable, it can disrupt important patterns of patient care. Imagine the impact on obstetrics practice if oxytocin became unavailable due to manufacturing shortages. Likely, both market forces and government regulation are the root cause of the shortfalls. Preventing the adverse consequences of the sudden loss of key pharmaceuticals and devices is an important priority to ensure optimal care of our patients.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Suddenly, indigo carmine is in short supply throughout the United States. One manufacturer has stopped production because of a raw materials shortage; another is experiencing manufacturing delays. Neither company can estimate a resupply or product return date.¹

Indigo carmine is approved by the US Food and Drug Administration (FDA) to localize ureteral orifices during cystoscopy and is commonly used in obstetrics and gynecology as a marker dye in the following additional situations:

• administered in a dilute solution via a catheter to back fill the bladder and test for bladder injury
• administered via a cannula in the uterine cavity to test the patency of the fallopian tubes
• injected into the amniotic fluid compartment to test for premature rupture of the membranes (PROM)
• injected into the amniotic fluid of a twin gestation to mark the amniotic fluid of one twin.

With this agent in short supply, we need to identify alternative marker dyes to use in our clinical practice. In this editorial, I provide a list of possible options to replace indigo carmine. Evidence supporting the use and safety of marker dyes in obstetrics and gynecology is based on small cohorts or case reports. The available evidence is of modest to low quality, and it is especially challenging to identify uncommon adverse effects. Consequently, expert opinion guides most practice recommendations.

Options to test the function of the ureters at cystoscopy
Given the lack of availability of indigo carmine, I recommend one of the following three options to test the function of the ureters at cystoscopy.

Partially fill the bladder with a solution of either sterile water or a 10% dextrose solution. (Experienced surgeons may prefer to use saline.) The turbulence of the interaction between the ureteral urine jet and instilled fluid in the bladder may permit visualization of the urine stream exiting the ureteral orifices as it swirls through the sterile water or dextrose solution. Both sterile water and a 10% dextrose solution offer a contrast in viscosity between the urine and the cystoscopy fluid, which may enhance the ability to detect the urine jet leaving the ureter.²

Administer IV methylene blue. Methylene blue is FDA approved for methemoglobinemia treatment. For this indication, it is administered intravenously at a dose of 1 to 2 mg/kgover 5 to 10 minutes. Paradoxically, when administered at a dose of >7 mg/kg, methylene blue can cause methemoglobinemia.³

Methylene blue often is provided as a 1% solution of 10 mg/mL in 10-mL vials. To use intravenous (IV) methylene blue to test ureteral function at cystoscopy, administer IV methylene blue 50 mg over 5 minutes. Use the cystoscope to view the colored urine exiting the ureteral orifices.^4,5 Administering a small dose of IV furosemide may accelerate the appearance of methylene blue in the urine.

When to use caution. Methylene blue blocks serotonin metabolism by inhibiting monoamine oxidase and may precipitate a serotonin syndrome in patients taking selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs).

Common findings in the serotonin syndrome include: temperature above 38° C (100.4° F), anxiety, agitation, delirium, clonus, tremor, and hypertonia.⁶ I recommend that you DO NOT use IV methylene blue in patients taking these medications.^7,8

Great caution should be used before administering IV methylene blue in the presence of the following clinical situations:

• renal impairment  
• G6PD deficiency
• pediatric patients.

Methylene blue never should be given by a subcutaneous or intrathecal route. In pregnant women it should never be injected into the amniotic fluid compartment.

Use preoperative oral phenazo-pyridine. If the preoperative plan includes a cystoscopy procedure to test ureteral function, administering oral phenazopyridine in the preoperative holding area will result in colorization of the urine within 30 minutes, and it will persist for approximately 4 to 5 hours. To use this approach, administer one dose of phenazopyridine (Pyridium, Azo-Gesic), 100 mg or 200 mg orally, 30 minutes to 1 hour before the planned surgical start time, in the preoperative holding area.⁹ During cystoscopy, the urine from the ureteral jet will be colored orange.

When to use caution. Phenazo­pyridine should not be administered to patients with G6PD deficiency.

Option to test for bladder injury
Methylene blue. If methylene blue is used to test the integrity of the bladder, I recommend diluting 10 mg methylene blue in 1 L normal saline and then instilling the dilute solution through a catheter into the bladder.¹⁰

It is unlikely that this technique will be associated with sufficient methylene blue absorption to cause a serotonin syndrome. Therefore, this technique can be used in patients taking SSRIs, SNRIs, and MAOIs.

Option to test patency of the fallopian tubes (chromopertubation)
Methylene blue. If methylene blue is used via a cannula in the uterine cavity to test the patency of the fallopian tubes, I recommend diluting 10 mg methylene blue in 150 mL normal saline and using the dilute solution to test tubal patency.

It is unlikely that this process will lead to sufficient methylene blue absorption to cause a serotonin syndrome. Therefore, this technique can be used in patients taking SSRIs, SNRIs and MAOIs. However, if intrauterine injection of the dilute dye solution results in extravasation of the dye into the pelvic veins, a significant amount of dye can enter the circulation.¹¹ There are case reports of anaphylaxis following intrauterine injection of methylene blue to test tubal patency.^12,13

Options to diagnose PROM and to use for twin amniocentesis
None. Most experts recommend against the intra-amniotic injection of methylene blue to diagnose PROM or in twin amniocentesis procedures. Methylene blue injected into the intra-amniotic fluid during amniocentesis in multiple gestations has been reported to cause fetal bowel obstruction or atresia.^14,15 Fetal death also has been reported.¹⁶ Decades ago, indocyanine green, which is FDA approved to determine cardiac output, liver blood flow, and hepatic function, was reported to be useful to mark one sac of a twin gestation during amniocentesis.¹⁷ With modern ultrasonography technology, the need to rely on a dye to mark a sac of a twin has decreased significantly.

Our only option is to cope—effectively as possible Over decades, the medical community develops patterns of patient care that are critically dependent on the availability of key pharmaceuticals and devices. When a pharmaceutical or device suddenly becomes unavailable, it can disrupt important patterns of patient care. Imagine the impact on obstetrics practice if oxytocin became unavailable due to manufacturing shortages. Likely, both market forces and government regulation are the root cause of the shortfalls. Preventing the adverse consequences of the sudden loss of key pharmaceuticals and devices is an important priority to ensure optimal care of our patients.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Suddenly, indigo carmine is in short supply throughout the United States. One manufacturer has stopped production because of a raw materials shortage; another is experiencing manufacturing delays. Neither company can estimate a resupply or product return date.¹

Indigo carmine is approved by the US Food and Drug Administration (FDA) to localize ureteral orifices during cystoscopy and is commonly used in obstetrics and gynecology as a marker dye in the following additional situations:

• administered in a dilute solution via a catheter to back fill the bladder and test for bladder injury
• administered via a cannula in the uterine cavity to test the patency of the fallopian tubes
• injected into the amniotic fluid compartment to test for premature rupture of the membranes (PROM)
• injected into the amniotic fluid of a twin gestation to mark the amniotic fluid of one twin.

With this agent in short supply, we need to identify alternative marker dyes to use in our clinical practice. In this editorial, I provide a list of possible options to replace indigo carmine. Evidence supporting the use and safety of marker dyes in obstetrics and gynecology is based on small cohorts or case reports. The available evidence is of modest to low quality, and it is especially challenging to identify uncommon adverse effects. Consequently, expert opinion guides most practice recommendations.

Options to test the function of the ureters at cystoscopy
Given the lack of availability of indigo carmine, I recommend one of the following three options to test the function of the ureters at cystoscopy.

Partially fill the bladder with a solution of either sterile water or a 10% dextrose solution. (Experienced surgeons may prefer to use saline.) The turbulence of the interaction between the ureteral urine jet and instilled fluid in the bladder may permit visualization of the urine stream exiting the ureteral orifices as it swirls through the sterile water or dextrose solution. Both sterile water and a 10% dextrose solution offer a contrast in viscosity between the urine and the cystoscopy fluid, which may enhance the ability to detect the urine jet leaving the ureter.²

Administer IV methylene blue. Methylene blue is FDA approved for methemoglobinemia treatment. For this indication, it is administered intravenously at a dose of 1 to 2 mg/kgover 5 to 10 minutes. Paradoxically, when administered at a dose of >7 mg/kg, methylene blue can cause methemoglobinemia.³

Methylene blue often is provided as a 1% solution of 10 mg/mL in 10-mL vials. To use intravenous (IV) methylene blue to test ureteral function at cystoscopy, administer IV methylene blue 50 mg over 5 minutes. Use the cystoscope to view the colored urine exiting the ureteral orifices.^4,5 Administering a small dose of IV furosemide may accelerate the appearance of methylene blue in the urine.

When to use caution. Methylene blue blocks serotonin metabolism by inhibiting monoamine oxidase and may precipitate a serotonin syndrome in patients taking selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs).

Common findings in the serotonin syndrome include: temperature above 38° C (100.4° F), anxiety, agitation, delirium, clonus, tremor, and hypertonia.⁶ I recommend that you DO NOT use IV methylene blue in patients taking these medications.^7,8

Great caution should be used before administering IV methylene blue in the presence of the following clinical situations:

• renal impairment  
• G6PD deficiency
• pediatric patients.

Methylene blue never should be given by a subcutaneous or intrathecal route. In pregnant women it should never be injected into the amniotic fluid compartment.

Use preoperative oral phenazo-pyridine. If the preoperative plan includes a cystoscopy procedure to test ureteral function, administering oral phenazopyridine in the preoperative holding area will result in colorization of the urine within 30 minutes, and it will persist for approximately 4 to 5 hours. To use this approach, administer one dose of phenazopyridine (Pyridium, Azo-Gesic), 100 mg or 200 mg orally, 30 minutes to 1 hour before the planned surgical start time, in the preoperative holding area.⁹ During cystoscopy, the urine from the ureteral jet will be colored orange.

When to use caution. Phenazo­pyridine should not be administered to patients with G6PD deficiency.

Option to test for bladder injury
Methylene blue. If methylene blue is used to test the integrity of the bladder, I recommend diluting 10 mg methylene blue in 1 L normal saline and then instilling the dilute solution through a catheter into the bladder.¹⁰

It is unlikely that this technique will be associated with sufficient methylene blue absorption to cause a serotonin syndrome. Therefore, this technique can be used in patients taking SSRIs, SNRIs, and MAOIs.

Option to test patency of the fallopian tubes (chromopertubation)
Methylene blue. If methylene blue is used via a cannula in the uterine cavity to test the patency of the fallopian tubes, I recommend diluting 10 mg methylene blue in 150 mL normal saline and using the dilute solution to test tubal patency.

It is unlikely that this process will lead to sufficient methylene blue absorption to cause a serotonin syndrome. Therefore, this technique can be used in patients taking SSRIs, SNRIs and MAOIs. However, if intrauterine injection of the dilute dye solution results in extravasation of the dye into the pelvic veins, a significant amount of dye can enter the circulation.¹¹ There are case reports of anaphylaxis following intrauterine injection of methylene blue to test tubal patency.^12,13

Options to diagnose PROM and to use for twin amniocentesis
None. Most experts recommend against the intra-amniotic injection of methylene blue to diagnose PROM or in twin amniocentesis procedures. Methylene blue injected into the intra-amniotic fluid during amniocentesis in multiple gestations has been reported to cause fetal bowel obstruction or atresia.^14,15 Fetal death also has been reported.¹⁶ Decades ago, indocyanine green, which is FDA approved to determine cardiac output, liver blood flow, and hepatic function, was reported to be useful to mark one sac of a twin gestation during amniocentesis.¹⁷ With modern ultrasonography technology, the need to rely on a dye to mark a sac of a twin has decreased significantly.

Our only option is to cope—effectively as possible Over decades, the medical community develops patterns of patient care that are critically dependent on the availability of key pharmaceuticals and devices. When a pharmaceutical or device suddenly becomes unavailable, it can disrupt important patterns of patient care. Imagine the impact on obstetrics practice if oxytocin became unavailable due to manufacturing shortages. Likely, both market forces and government regulation are the root cause of the shortfalls. Preventing the adverse consequences of the sudden loss of key pharmaceuticals and devices is an important priority to ensure optimal care of our patients.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Click here to register for PAGS 2014 December 4 to 6 at the Bellagio in Las Vegas

More from PAGS 2013:

Lichen sclerosis: My approach to treatment
Michael Baggish, MD

Click here to register for PAGS 2014 December 4 to 6 at the Bellagio in Las Vegas

More from PAGS 2013:

Lichen sclerosis: My approach to treatment
Michael Baggish, MD

Click here to register for PAGS 2014 December 4 to 6 at the Bellagio in Las Vegas

More from PAGS 2013:

Lichen sclerosis: My approach to treatment
Michael Baggish, MD

This year I focus on four interesting and clinically relevant studies:

• an article by Huang and colleagues addressing the important issue of how best to reduce the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infection in critically ill patients hospitalized in the intensive care unit (ICU)
• a study by Duggal and colleagues assessing the value of perioperative oxygen ­supplementation to reduce the frequency of postcesarean infection
• an investigation of diagnostic criteria for urinary tract infection (UTI) by Hooton and colleagues
• an exploration of the association between intra-amniotic inflammation, as distinct from bacterial colonization, and adverse fetal outcomes.

For ICU patients, universal decolonization reduces nosocomial infection more than targeted decolonization

Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255–2265.

Infection in general, and nosocomial infection in particular, is common among patients hospitalized in the ICU. Such patients often are severely immunosuppressed and debilitated. They are likely to have multiple indwelling catheters and to require mechanical ventilation—interventions that predispose to life-threatening infection. The longer the duration of care in the ICU, the greater the risk of infection, especially infection caused by organisms that have acquired resistance to multiple antibiotics.

In this cluster-randomized trial, Huang and colleagues compared targeted and universal decolonization of patients treated in an ICU to determine which approach was more effective at preventing nosocomial infection, particularly MRSA infection. They found universal decolonization to be superior to targeted decolonization in reducing these infections.

Details of the studyInvestigators conducted their study in 74 ICUs in 43 hospitals. Each hospital was ­randomly assigned to one of three interventions:

• Group 1: MRSA screening followed by isolation of colonized patients
• Group 2: MRSA screening followed by isolation and decolonization of MRSA carriers
• Group 3: Universal decolonization (no screening).

The decolonization regimen consisted of twice-daily administration of intranasal mupirocin for 5 days and daily bathing with chlorhexidine-impregnated cloths for the duration of the ICU stay.

The study’s two endpoints were 1) the modeled hazard ratios for MRSA clinical isolates and 2) the hazard ratios for bloodstream infection with any pathogen.

During the intervention period, fewer MRSA isolates were found in the universal decolonization group, compared with the other two groups (P<.01). In addition, the number of bloodstream infections in the universal decolonization group was significantly lower than in the other two groups (P<.001). Fifty-four patients (number needed to treat) needed to undergo decolonization to prevent one bloodstream infection.

What this EVIDENCE means for practiceThe relevance of this investigation for those of us in the field of obstetrics and gynecology is simple and clear: If we have to transfer a patient to an ICU (such as an HIV-infected patient with a serious post­cesarean infection, or an oncology patient with a badly infected surgical wound), she should immediately be started on a regimen of twice-daily nasal mupirocin and daily bathing with chlorhexidine. This straightforward intervention will be of great value in reducing the incidence of bacteremia caused by a particularly dangerous pathogen.

Related article: Update on infectious disease. Patrick Duff, MD (July 2013)

The jury is still out on supplemental oxygen to reduce surgical site infection

Duggal N, Poddatorri V, Noroozkhani S, Siddik-Ahman RI, Caughey AB. Perioperative oxygen supplementation and surgical site infection after cesarean delivery. Obstet Gynecol. 2013;122(1):79–84.

In a widely read study published in 2000 in the New England Journal of Medicine, Greif and colleagues demonstrated that, in patients undergoing colorectal surgery, the rate of postoperative wound infection was significantly reduced from 11.2% in patients given 30% supplemental oxygen during surgery to 5.2% in those given 80% supplemental oxygen.¹ The oxygen was continued for 2 hours after surgery.

In a later study among general surgery patients, Pryor and colleagues were unable to replicate this finding.² It was in this setting that Duggal and colleagues undertook their investigation among women undergoing cesarean delivery. These investigators, too, were unable to replicate the 2000 finding of Greif and colleagues.

Related article: Update: Infectious Disease.  Patrick Duff, MD (June 2012)

Details of the studyOver 4 years, from 2006 to 2010, Duggal and colleagues conducted a prospective, randomized, double-blinded controlled trial among patients undergoing scheduled, urgent, or emergent cesarean delivery. All patients were given prophylactic antibiotics, usually cefazolin 2 g intravenously after the infant’s umbilical cord was clamped. Surgical technique was reasonably well standardized and included closure of the deep subcutaneous layer of tissue using 2-0 plain gut sutures.

Patients were randomly assigned to receive supplemental oxygen via face mask, at 30% or 80% concentration, during surgery and for 1 hour postoperatively. They were evaluated postoperatively at 2 and 6 weeks. The primary outcome measure was a composite of surgical site infection, endometritis, or both.

A total of 415 women received 30% oxygen and 416 were given 80% oxygen. The two groups were well matched for important confounding variables such as age, race, pari­ty, body mass index, number of prior cesarean deliveries, diabetes, cardiopulmonary disease, anemia, smoking, and chronic steroid use.

The groups did not differ in the frequency of surgical site infection or endometritis, which occurred at a rate of 2.4% in the group receiving 30% oxygen, compared with 2.9% in the group given 80% oxygen.

Rationale for oxygen supplementationAdequate tissue oxygenation has been observed to enhance the bactericidal function of neutrophils. So why were Duggal and colleagues unable to demonstrate a beneficial effect for oxygen therapy?

The most likely explanations:

• Their obstetric patients were less seriously ill than the general surgery patients undergoing colorectal surgery in the study by Greif and colleagues.
• Given the low overall rate of infection, their sample size may have been too small to show a statistically significant difference in outcome (Type II statistical error).

In point of fact, more than 80% of patients in both groups had scheduled cesarean deliveries, presumably prior to the onset of labor and ruptured membranes. The outcome may have been different had the groups included a majority of patients undergoing surgery after labor and ruptured membranes.

What this EVIDENCE means for practiceUntil additional studies are performed, I cannot recommend routine use of perioperative hyperoxygenation as a method of reducing the rate of surgical site infection and/or endometritis. However, we have very good scientific evidence indicating that the following measures significantly reduce the rate of endometritis after both scheduled and unscheduled cesarean delivery:
• administration of prophylactic antibiotics prior to the start of surgery
• removal of the placenta by gentle traction on the umbilical cord rather than by manual extraction.^3,4
Similarly, we have sound evidence demonstrating that the following measures significantly reduce the rate of surgical site infection:
• clipping, rather than shaving, the hair at the surgical site just prior to the incision
• preoperative cleansing of the surgical area with chlorhexidine
• administration of prophylactic antibiotics prior to the start of surgery closure of the lower half of the subcutaneous tissue (if it exceeds 2 cm in thickness) using a relatively noninflammatory suture such as polyglactin or polyglycolic acid.

The presence of E coli in a midstream urine specimen is highly predictive of UTI

Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013;369(20):1883–1891.

Urinary tract infections (UTI) are among the most common infections experienced by women of all ages. Asymptomatic bacteriuria affects 5% to 10% of all sexually active women. During the course of their lifetime, at least 50% of women develop some form of UTI.

Pyelonephritis is not nearly as common as asymptomatic bacteriuria or cystitis, but this infection can be especially dangerous in older, debilitated women who reside in nursing homes and require indwelling catheters.

The most common organisms that cause UTIs in women are the aerobic gram-negative bacilli, principally Escherichia coli, Klebsiella species, and Proteus species. Other Gram-negative bacilli such as Pseudomonas species, Serratia, or Enterobacter are not common uropathogens except in immunosuppressed hosts or patients who have long-term indwelling catheters. Gram-positive organisms such as group B streptococci, enterococci, and staphylococcal species are occasional pathogens but, as Hooton and colleagues demonstrate in this study, perhaps not quite as important as we once thought.

Related articles:
• Update on infectious disease. Alan T. N. Tita, MD, PhD (June 2011)
• Have you tried these innovative alternatives to antibiotics for UTI prevention? Patrick A. Nosti, MD; Kate C. Arnold; Cheryl B. Iglesia, MD (February 2013)

Details of the studyUsing an elegantly simple design, the Hooton team studied women aged 18 to 49 years who had symptoms suggestive of acute cystitis. They collected two urine specimens from each woman for culture—one was collected using the midstream, clean-catch technique and the other by catheterization. They then compared microbial species and colony counts in the paired specimens to determine the positive and negative predictive values of midstream culture results, using the catheterized culture results as the reference standard.

The 226 women in the study experienced 236 clinical episodes suggestive of acute cystitis. One hundred forty-two (70%) of the catheterized specimens were positive for infection; of these, four specimens yielded more than one uropathogen. One hundred fifty-seven (78%) of the midstream specimens were positive for infection.

The presence of E coli in the midstream culture was highly predictive of a positive culture for E coli by catheterization, even when the cutoff was only 100 colonies/mL on the midstream specimen (positive predictive value, 93%). However, neither the presence of enterococci nor the presence of group B streptococci, at any colony count, was predictive of a positive culture by catheterization. Interestingly, among 41 patients who had either enterococci or group B streptococci in their midstream culture, E coli was present in the catheterizedculture in 61% of cases, suggesting that infection with E coli may be the more important cause of the patient’s symptoms.

Hooton and colleagues concluded that the presence of E coli on a midstream culture, even in low colony counts, is predictive of true bladder infection, as determined by catheterization. However, enterococci and group B streptococci were more likely to be vaginal contaminants or associated with coinfection with E coli, or bot.

What this EVIDENCE means for practiceThe findings of Hooton and colleagues have several key implications for practicing clinicians:
• When either a pregnant or nonpregnant patient experiences her first episode of acute cystitis, the overwhelming probability is that E coli is the infecting pathogen. We can reduce costs by empirically treating the initial infection, thereby avoiding the expense of a urine culture.
• For patients with recurrent infections or for immunocompromised patients, a culture and sensitivity test should be performed because other uropathogens are more likely to be involved and may have less predictable antibiotic susceptibility patterns.
• Contamination of supposed “clean-catch” specimens is very common, and the cultures resulting from these specimens can mislead us in our decisions about antibiotic therapy. Enterococci and group B streptococci are more likely than not to be contaminants from the vaginal flora rather than true infecting pathogens. When they are present in the bladder, they are usually associated with E coli. Accordingly, E coli should be the principal target of anti­biotic therapy.
• To avoid concerns about contamination of specimens in acutely symptomatic patients, obtain the urine specimen by catheter. In the catheterized specimen, the cutoff for true bladder infection should be ≥100 colonies/mL. The cutoff of ≥100,000 colonies/mLis applicable only for clean-catch specimens obtained from asymptomatic patients.
• Clinical laboratories should embrace the new cutoff and report even seemingly low colony counts when the urine sample has been obtained by catheterization.

In preterm labor, amniotic fluid infection without inflammation does not necessarily predict a poor fetal outcome

Combs CA, Gravett M, Garite TJ, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;210(2):125.e1–e15.

In this very important clinical investigation, Combs and colleagues collected amniotic fluid from 305 women with preterm labor. They then measured the amniotic fluid concentration of interleukin-6 (IL-6) and assessed for the presence of microbial invasion of the amniotic cavity (MIAC) by either culture or detection of microbial 16S ribosomal DNA. Based on these test results, investigators divided the patients into five groups:

• Infection—defined as positive MIAC and IL-6 >11.3 ng/mL
• Severe inflammation—negative MIAC and IL-6 >11.3 ng/mL
• Mild inflammation—no MIAC and IL-6 from 2.6 to 11.2 ng/mL
• Colonization—positive MIAC and IL-6 <2.6 ng/mL
• Negative—no MIAC and IL-6 <2.6 ng/mL.

The end points of the investigation were latency period and composite perinatal morbidity and mortality. Perinatal morbidity included respiratory distress syndrome, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, and culture-proven neonatal sepsis.

Related article: Does treating asymptomatic bacterial vaginosis reduce preterm delivery? Hyagriv N. Simhan, MD, MSCR (Examining the Evidence; April 2008)

Interestingly, the infection and severe inflammation groups had similar short latency periods (median of <1 and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively).

The colonization and negative groups also had similar latency periods (median of 23.5 and 25 days, respectively) and similar rates of composite morbidity and mortality (21% and 25%, respectively).

The mild inflammation group had intermediate outcomes.

When Combs and colleagues used multivariate analysis to adjust for gestational age at enrollment, amniotic fluid IL-6 concentrations greater than 11.3 ng/mL and in the range of 2.6 to 11.3 ng/mL—but not MIAC—were associated with increased composite perinatal morbidity and mortality.

What this EVIDENCE means for practiceThis study offers several critically important take-home messages:
• Bacterial colonization of the amniotic fluid, without actual inflammation, is not necessarily associated with an ominous outcome for the fetus
• Varying degrees of inflammation exist
• The more intense the inflammation, the worse the outcome for the baby
• The logical clinical application of this investigation is to modify our practice so that, when we perform an amniocentesis for patients with preterm labor, we look not only for bacterial growth but for the presence of key inflammatory mediators in the amniotic fluid, such as IL-6
• A rapidly available, inexpensive, and easy-to-perform assay for IL-6 would be invaluable in improving our ability to assess patients for subclinical infection and inflammation
• An important question, of course, is whether early implementation of specific anti-inflammatory therapy could alter the prognosis for the fetus in selected cases.

WE WANT TO HEAR FROM YOU! Share your thoughts on this article. Send your Letter to the Editor to: [email protected]

This year I focus on four interesting and clinically relevant studies:

• an article by Huang and colleagues addressing the important issue of how best to reduce the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infection in critically ill patients hospitalized in the intensive care unit (ICU)
• a study by Duggal and colleagues assessing the value of perioperative oxygen ­supplementation to reduce the frequency of postcesarean infection
• an investigation of diagnostic criteria for urinary tract infection (UTI) by Hooton and colleagues
• an exploration of the association between intra-amniotic inflammation, as distinct from bacterial colonization, and adverse fetal outcomes.

For ICU patients, universal decolonization reduces nosocomial infection more than targeted decolonization

Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255–2265.

Infection in general, and nosocomial infection in particular, is common among patients hospitalized in the ICU. Such patients often are severely immunosuppressed and debilitated. They are likely to have multiple indwelling catheters and to require mechanical ventilation—interventions that predispose to life-threatening infection. The longer the duration of care in the ICU, the greater the risk of infection, especially infection caused by organisms that have acquired resistance to multiple antibiotics.

In this cluster-randomized trial, Huang and colleagues compared targeted and universal decolonization of patients treated in an ICU to determine which approach was more effective at preventing nosocomial infection, particularly MRSA infection. They found universal decolonization to be superior to targeted decolonization in reducing these infections.

Details of the studyInvestigators conducted their study in 74 ICUs in 43 hospitals. Each hospital was ­randomly assigned to one of three interventions:

• Group 1: MRSA screening followed by isolation of colonized patients
• Group 2: MRSA screening followed by isolation and decolonization of MRSA carriers
• Group 3: Universal decolonization (no screening).

The decolonization regimen consisted of twice-daily administration of intranasal mupirocin for 5 days and daily bathing with chlorhexidine-impregnated cloths for the duration of the ICU stay.

The study’s two endpoints were 1) the modeled hazard ratios for MRSA clinical isolates and 2) the hazard ratios for bloodstream infection with any pathogen.

During the intervention period, fewer MRSA isolates were found in the universal decolonization group, compared with the other two groups (P<.01). In addition, the number of bloodstream infections in the universal decolonization group was significantly lower than in the other two groups (P<.001). Fifty-four patients (number needed to treat) needed to undergo decolonization to prevent one bloodstream infection.

What this EVIDENCE means for practiceThe relevance of this investigation for those of us in the field of obstetrics and gynecology is simple and clear: If we have to transfer a patient to an ICU (such as an HIV-infected patient with a serious post­cesarean infection, or an oncology patient with a badly infected surgical wound), she should immediately be started on a regimen of twice-daily nasal mupirocin and daily bathing with chlorhexidine. This straightforward intervention will be of great value in reducing the incidence of bacteremia caused by a particularly dangerous pathogen.

Related article: Update on infectious disease. Patrick Duff, MD (July 2013)

The jury is still out on supplemental oxygen to reduce surgical site infection

Duggal N, Poddatorri V, Noroozkhani S, Siddik-Ahman RI, Caughey AB. Perioperative oxygen supplementation and surgical site infection after cesarean delivery. Obstet Gynecol. 2013;122(1):79–84.

In a widely read study published in 2000 in the New England Journal of Medicine, Greif and colleagues demonstrated that, in patients undergoing colorectal surgery, the rate of postoperative wound infection was significantly reduced from 11.2% in patients given 30% supplemental oxygen during surgery to 5.2% in those given 80% supplemental oxygen.¹ The oxygen was continued for 2 hours after surgery.

In a later study among general surgery patients, Pryor and colleagues were unable to replicate this finding.² It was in this setting that Duggal and colleagues undertook their investigation among women undergoing cesarean delivery. These investigators, too, were unable to replicate the 2000 finding of Greif and colleagues.

Related article: Update: Infectious Disease.  Patrick Duff, MD (June 2012)

Details of the studyOver 4 years, from 2006 to 2010, Duggal and colleagues conducted a prospective, randomized, double-blinded controlled trial among patients undergoing scheduled, urgent, or emergent cesarean delivery. All patients were given prophylactic antibiotics, usually cefazolin 2 g intravenously after the infant’s umbilical cord was clamped. Surgical technique was reasonably well standardized and included closure of the deep subcutaneous layer of tissue using 2-0 plain gut sutures.

Patients were randomly assigned to receive supplemental oxygen via face mask, at 30% or 80% concentration, during surgery and for 1 hour postoperatively. They were evaluated postoperatively at 2 and 6 weeks. The primary outcome measure was a composite of surgical site infection, endometritis, or both.

A total of 415 women received 30% oxygen and 416 were given 80% oxygen. The two groups were well matched for important confounding variables such as age, race, pari­ty, body mass index, number of prior cesarean deliveries, diabetes, cardiopulmonary disease, anemia, smoking, and chronic steroid use.

The groups did not differ in the frequency of surgical site infection or endometritis, which occurred at a rate of 2.4% in the group receiving 30% oxygen, compared with 2.9% in the group given 80% oxygen.

Rationale for oxygen supplementationAdequate tissue oxygenation has been observed to enhance the bactericidal function of neutrophils. So why were Duggal and colleagues unable to demonstrate a beneficial effect for oxygen therapy?

The most likely explanations:

• Their obstetric patients were less seriously ill than the general surgery patients undergoing colorectal surgery in the study by Greif and colleagues.
• Given the low overall rate of infection, their sample size may have been too small to show a statistically significant difference in outcome (Type II statistical error).

In point of fact, more than 80% of patients in both groups had scheduled cesarean deliveries, presumably prior to the onset of labor and ruptured membranes. The outcome may have been different had the groups included a majority of patients undergoing surgery after labor and ruptured membranes.

What this EVIDENCE means for practiceUntil additional studies are performed, I cannot recommend routine use of perioperative hyperoxygenation as a method of reducing the rate of surgical site infection and/or endometritis. However, we have very good scientific evidence indicating that the following measures significantly reduce the rate of endometritis after both scheduled and unscheduled cesarean delivery:
• administration of prophylactic antibiotics prior to the start of surgery
• removal of the placenta by gentle traction on the umbilical cord rather than by manual extraction.^3,4
Similarly, we have sound evidence demonstrating that the following measures significantly reduce the rate of surgical site infection:
• clipping, rather than shaving, the hair at the surgical site just prior to the incision
• preoperative cleansing of the surgical area with chlorhexidine
• administration of prophylactic antibiotics prior to the start of surgery closure of the lower half of the subcutaneous tissue (if it exceeds 2 cm in thickness) using a relatively noninflammatory suture such as polyglactin or polyglycolic acid.

The presence of E coli in a midstream urine specimen is highly predictive of UTI

Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013;369(20):1883–1891.

Urinary tract infections (UTI) are among the most common infections experienced by women of all ages. Asymptomatic bacteriuria affects 5% to 10% of all sexually active women. During the course of their lifetime, at least 50% of women develop some form of UTI.

Pyelonephritis is not nearly as common as asymptomatic bacteriuria or cystitis, but this infection can be especially dangerous in older, debilitated women who reside in nursing homes and require indwelling catheters.

The most common organisms that cause UTIs in women are the aerobic gram-negative bacilli, principally Escherichia coli, Klebsiella species, and Proteus species. Other Gram-negative bacilli such as Pseudomonas species, Serratia, or Enterobacter are not common uropathogens except in immunosuppressed hosts or patients who have long-term indwelling catheters. Gram-positive organisms such as group B streptococci, enterococci, and staphylococcal species are occasional pathogens but, as Hooton and colleagues demonstrate in this study, perhaps not quite as important as we once thought.

Related articles:
• Update on infectious disease. Alan T. N. Tita, MD, PhD (June 2011)
• Have you tried these innovative alternatives to antibiotics for UTI prevention? Patrick A. Nosti, MD; Kate C. Arnold; Cheryl B. Iglesia, MD (February 2013)

Details of the studyUsing an elegantly simple design, the Hooton team studied women aged 18 to 49 years who had symptoms suggestive of acute cystitis. They collected two urine specimens from each woman for culture—one was collected using the midstream, clean-catch technique and the other by catheterization. They then compared microbial species and colony counts in the paired specimens to determine the positive and negative predictive values of midstream culture results, using the catheterized culture results as the reference standard.

The 226 women in the study experienced 236 clinical episodes suggestive of acute cystitis. One hundred forty-two (70%) of the catheterized specimens were positive for infection; of these, four specimens yielded more than one uropathogen. One hundred fifty-seven (78%) of the midstream specimens were positive for infection.

The presence of E coli in the midstream culture was highly predictive of a positive culture for E coli by catheterization, even when the cutoff was only 100 colonies/mL on the midstream specimen (positive predictive value, 93%). However, neither the presence of enterococci nor the presence of group B streptococci, at any colony count, was predictive of a positive culture by catheterization. Interestingly, among 41 patients who had either enterococci or group B streptococci in their midstream culture, E coli was present in the catheterizedculture in 61% of cases, suggesting that infection with E coli may be the more important cause of the patient’s symptoms.

Hooton and colleagues concluded that the presence of E coli on a midstream culture, even in low colony counts, is predictive of true bladder infection, as determined by catheterization. However, enterococci and group B streptococci were more likely to be vaginal contaminants or associated with coinfection with E coli, or bot.

What this EVIDENCE means for practiceThe findings of Hooton and colleagues have several key implications for practicing clinicians:
• When either a pregnant or nonpregnant patient experiences her first episode of acute cystitis, the overwhelming probability is that E coli is the infecting pathogen. We can reduce costs by empirically treating the initial infection, thereby avoiding the expense of a urine culture.
• For patients with recurrent infections or for immunocompromised patients, a culture and sensitivity test should be performed because other uropathogens are more likely to be involved and may have less predictable antibiotic susceptibility patterns.
• Contamination of supposed “clean-catch” specimens is very common, and the cultures resulting from these specimens can mislead us in our decisions about antibiotic therapy. Enterococci and group B streptococci are more likely than not to be contaminants from the vaginal flora rather than true infecting pathogens. When they are present in the bladder, they are usually associated with E coli. Accordingly, E coli should be the principal target of anti­biotic therapy.
• To avoid concerns about contamination of specimens in acutely symptomatic patients, obtain the urine specimen by catheter. In the catheterized specimen, the cutoff for true bladder infection should be ≥100 colonies/mL. The cutoff of ≥100,000 colonies/mLis applicable only for clean-catch specimens obtained from asymptomatic patients.
• Clinical laboratories should embrace the new cutoff and report even seemingly low colony counts when the urine sample has been obtained by catheterization.

In preterm labor, amniotic fluid infection without inflammation does not necessarily predict a poor fetal outcome

Combs CA, Gravett M, Garite TJ, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;210(2):125.e1–e15.

In this very important clinical investigation, Combs and colleagues collected amniotic fluid from 305 women with preterm labor. They then measured the amniotic fluid concentration of interleukin-6 (IL-6) and assessed for the presence of microbial invasion of the amniotic cavity (MIAC) by either culture or detection of microbial 16S ribosomal DNA. Based on these test results, investigators divided the patients into five groups:

• Infection—defined as positive MIAC and IL-6 >11.3 ng/mL
• Severe inflammation—negative MIAC and IL-6 >11.3 ng/mL
• Mild inflammation—no MIAC and IL-6 from 2.6 to 11.2 ng/mL
• Colonization—positive MIAC and IL-6 <2.6 ng/mL
• Negative—no MIAC and IL-6 <2.6 ng/mL.

The end points of the investigation were latency period and composite perinatal morbidity and mortality. Perinatal morbidity included respiratory distress syndrome, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, and culture-proven neonatal sepsis.

Related article: Does treating asymptomatic bacterial vaginosis reduce preterm delivery? Hyagriv N. Simhan, MD, MSCR (Examining the Evidence; April 2008)

Interestingly, the infection and severe inflammation groups had similar short latency periods (median of <1 and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively).

The colonization and negative groups also had similar latency periods (median of 23.5 and 25 days, respectively) and similar rates of composite morbidity and mortality (21% and 25%, respectively).

The mild inflammation group had intermediate outcomes.

When Combs and colleagues used multivariate analysis to adjust for gestational age at enrollment, amniotic fluid IL-6 concentrations greater than 11.3 ng/mL and in the range of 2.6 to 11.3 ng/mL—but not MIAC—were associated with increased composite perinatal morbidity and mortality.

What this EVIDENCE means for practiceThis study offers several critically important take-home messages:
• Bacterial colonization of the amniotic fluid, without actual inflammation, is not necessarily associated with an ominous outcome for the fetus
• Varying degrees of inflammation exist
• The more intense the inflammation, the worse the outcome for the baby
• The logical clinical application of this investigation is to modify our practice so that, when we perform an amniocentesis for patients with preterm labor, we look not only for bacterial growth but for the presence of key inflammatory mediators in the amniotic fluid, such as IL-6
• A rapidly available, inexpensive, and easy-to-perform assay for IL-6 would be invaluable in improving our ability to assess patients for subclinical infection and inflammation
• An important question, of course, is whether early implementation of specific anti-inflammatory therapy could alter the prognosis for the fetus in selected cases.

WE WANT TO HEAR FROM YOU! Share your thoughts on this article. Send your Letter to the Editor to: [email protected]

This year I focus on four interesting and clinically relevant studies:

• an article by Huang and colleagues addressing the important issue of how best to reduce the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infection in critically ill patients hospitalized in the intensive care unit (ICU)
• a study by Duggal and colleagues assessing the value of perioperative oxygen ­supplementation to reduce the frequency of postcesarean infection
• an investigation of diagnostic criteria for urinary tract infection (UTI) by Hooton and colleagues
• an exploration of the association between intra-amniotic inflammation, as distinct from bacterial colonization, and adverse fetal outcomes.

For ICU patients, universal decolonization reduces nosocomial infection more than targeted decolonization

Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255–2265.

Infection in general, and nosocomial infection in particular, is common among patients hospitalized in the ICU. Such patients often are severely immunosuppressed and debilitated. They are likely to have multiple indwelling catheters and to require mechanical ventilation—interventions that predispose to life-threatening infection. The longer the duration of care in the ICU, the greater the risk of infection, especially infection caused by organisms that have acquired resistance to multiple antibiotics.

In this cluster-randomized trial, Huang and colleagues compared targeted and universal decolonization of patients treated in an ICU to determine which approach was more effective at preventing nosocomial infection, particularly MRSA infection. They found universal decolonization to be superior to targeted decolonization in reducing these infections.

Details of the studyInvestigators conducted their study in 74 ICUs in 43 hospitals. Each hospital was ­randomly assigned to one of three interventions:

• Group 1: MRSA screening followed by isolation of colonized patients
• Group 2: MRSA screening followed by isolation and decolonization of MRSA carriers
• Group 3: Universal decolonization (no screening).

The decolonization regimen consisted of twice-daily administration of intranasal mupirocin for 5 days and daily bathing with chlorhexidine-impregnated cloths for the duration of the ICU stay.

The study’s two endpoints were 1) the modeled hazard ratios for MRSA clinical isolates and 2) the hazard ratios for bloodstream infection with any pathogen.

During the intervention period, fewer MRSA isolates were found in the universal decolonization group, compared with the other two groups (P<.01). In addition, the number of bloodstream infections in the universal decolonization group was significantly lower than in the other two groups (P<.001). Fifty-four patients (number needed to treat) needed to undergo decolonization to prevent one bloodstream infection.

What this EVIDENCE means for practiceThe relevance of this investigation for those of us in the field of obstetrics and gynecology is simple and clear: If we have to transfer a patient to an ICU (such as an HIV-infected patient with a serious post­cesarean infection, or an oncology patient with a badly infected surgical wound), she should immediately be started on a regimen of twice-daily nasal mupirocin and daily bathing with chlorhexidine. This straightforward intervention will be of great value in reducing the incidence of bacteremia caused by a particularly dangerous pathogen.

Related article: Update on infectious disease. Patrick Duff, MD (July 2013)

The jury is still out on supplemental oxygen to reduce surgical site infection

Duggal N, Poddatorri V, Noroozkhani S, Siddik-Ahman RI, Caughey AB. Perioperative oxygen supplementation and surgical site infection after cesarean delivery. Obstet Gynecol. 2013;122(1):79–84.

In a widely read study published in 2000 in the New England Journal of Medicine, Greif and colleagues demonstrated that, in patients undergoing colorectal surgery, the rate of postoperative wound infection was significantly reduced from 11.2% in patients given 30% supplemental oxygen during surgery to 5.2% in those given 80% supplemental oxygen.¹ The oxygen was continued for 2 hours after surgery.

In a later study among general surgery patients, Pryor and colleagues were unable to replicate this finding.² It was in this setting that Duggal and colleagues undertook their investigation among women undergoing cesarean delivery. These investigators, too, were unable to replicate the 2000 finding of Greif and colleagues.

Related article: Update: Infectious Disease.  Patrick Duff, MD (June 2012)

Details of the studyOver 4 years, from 2006 to 2010, Duggal and colleagues conducted a prospective, randomized, double-blinded controlled trial among patients undergoing scheduled, urgent, or emergent cesarean delivery. All patients were given prophylactic antibiotics, usually cefazolin 2 g intravenously after the infant’s umbilical cord was clamped. Surgical technique was reasonably well standardized and included closure of the deep subcutaneous layer of tissue using 2-0 plain gut sutures.

Patients were randomly assigned to receive supplemental oxygen via face mask, at 30% or 80% concentration, during surgery and for 1 hour postoperatively. They were evaluated postoperatively at 2 and 6 weeks. The primary outcome measure was a composite of surgical site infection, endometritis, or both.

A total of 415 women received 30% oxygen and 416 were given 80% oxygen. The two groups were well matched for important confounding variables such as age, race, pari­ty, body mass index, number of prior cesarean deliveries, diabetes, cardiopulmonary disease, anemia, smoking, and chronic steroid use.

The groups did not differ in the frequency of surgical site infection or endometritis, which occurred at a rate of 2.4% in the group receiving 30% oxygen, compared with 2.9% in the group given 80% oxygen.

Rationale for oxygen supplementationAdequate tissue oxygenation has been observed to enhance the bactericidal function of neutrophils. So why were Duggal and colleagues unable to demonstrate a beneficial effect for oxygen therapy?

The most likely explanations:

• Their obstetric patients were less seriously ill than the general surgery patients undergoing colorectal surgery in the study by Greif and colleagues.
• Given the low overall rate of infection, their sample size may have been too small to show a statistically significant difference in outcome (Type II statistical error).

In point of fact, more than 80% of patients in both groups had scheduled cesarean deliveries, presumably prior to the onset of labor and ruptured membranes. The outcome may have been different had the groups included a majority of patients undergoing surgery after labor and ruptured membranes.

What this EVIDENCE means for practiceUntil additional studies are performed, I cannot recommend routine use of perioperative hyperoxygenation as a method of reducing the rate of surgical site infection and/or endometritis. However, we have very good scientific evidence indicating that the following measures significantly reduce the rate of endometritis after both scheduled and unscheduled cesarean delivery:
• administration of prophylactic antibiotics prior to the start of surgery
• removal of the placenta by gentle traction on the umbilical cord rather than by manual extraction.^3,4
Similarly, we have sound evidence demonstrating that the following measures significantly reduce the rate of surgical site infection:
• clipping, rather than shaving, the hair at the surgical site just prior to the incision
• preoperative cleansing of the surgical area with chlorhexidine
• administration of prophylactic antibiotics prior to the start of surgery closure of the lower half of the subcutaneous tissue (if it exceeds 2 cm in thickness) using a relatively noninflammatory suture such as polyglactin or polyglycolic acid.

The presence of E coli in a midstream urine specimen is highly predictive of UTI

Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013;369(20):1883–1891.

Urinary tract infections (UTI) are among the most common infections experienced by women of all ages. Asymptomatic bacteriuria affects 5% to 10% of all sexually active women. During the course of their lifetime, at least 50% of women develop some form of UTI.

Pyelonephritis is not nearly as common as asymptomatic bacteriuria or cystitis, but this infection can be especially dangerous in older, debilitated women who reside in nursing homes and require indwelling catheters.

The most common organisms that cause UTIs in women are the aerobic gram-negative bacilli, principally Escherichia coli, Klebsiella species, and Proteus species. Other Gram-negative bacilli such as Pseudomonas species, Serratia, or Enterobacter are not common uropathogens except in immunosuppressed hosts or patients who have long-term indwelling catheters. Gram-positive organisms such as group B streptococci, enterococci, and staphylococcal species are occasional pathogens but, as Hooton and colleagues demonstrate in this study, perhaps not quite as important as we once thought.

Related articles:
• Update on infectious disease. Alan T. N. Tita, MD, PhD (June 2011)
• Have you tried these innovative alternatives to antibiotics for UTI prevention? Patrick A. Nosti, MD; Kate C. Arnold; Cheryl B. Iglesia, MD (February 2013)

Details of the studyUsing an elegantly simple design, the Hooton team studied women aged 18 to 49 years who had symptoms suggestive of acute cystitis. They collected two urine specimens from each woman for culture—one was collected using the midstream, clean-catch technique and the other by catheterization. They then compared microbial species and colony counts in the paired specimens to determine the positive and negative predictive values of midstream culture results, using the catheterized culture results as the reference standard.

The 226 women in the study experienced 236 clinical episodes suggestive of acute cystitis. One hundred forty-two (70%) of the catheterized specimens were positive for infection; of these, four specimens yielded more than one uropathogen. One hundred fifty-seven (78%) of the midstream specimens were positive for infection.

The presence of E coli in the midstream culture was highly predictive of a positive culture for E coli by catheterization, even when the cutoff was only 100 colonies/mL on the midstream specimen (positive predictive value, 93%). However, neither the presence of enterococci nor the presence of group B streptococci, at any colony count, was predictive of a positive culture by catheterization. Interestingly, among 41 patients who had either enterococci or group B streptococci in their midstream culture, E coli was present in the catheterizedculture in 61% of cases, suggesting that infection with E coli may be the more important cause of the patient’s symptoms.

Hooton and colleagues concluded that the presence of E coli on a midstream culture, even in low colony counts, is predictive of true bladder infection, as determined by catheterization. However, enterococci and group B streptococci were more likely to be vaginal contaminants or associated with coinfection with E coli, or bot.

What this EVIDENCE means for practiceThe findings of Hooton and colleagues have several key implications for practicing clinicians:
• When either a pregnant or nonpregnant patient experiences her first episode of acute cystitis, the overwhelming probability is that E coli is the infecting pathogen. We can reduce costs by empirically treating the initial infection, thereby avoiding the expense of a urine culture.
• For patients with recurrent infections or for immunocompromised patients, a culture and sensitivity test should be performed because other uropathogens are more likely to be involved and may have less predictable antibiotic susceptibility patterns.
• Contamination of supposed “clean-catch” specimens is very common, and the cultures resulting from these specimens can mislead us in our decisions about antibiotic therapy. Enterococci and group B streptococci are more likely than not to be contaminants from the vaginal flora rather than true infecting pathogens. When they are present in the bladder, they are usually associated with E coli. Accordingly, E coli should be the principal target of anti­biotic therapy.
• To avoid concerns about contamination of specimens in acutely symptomatic patients, obtain the urine specimen by catheter. In the catheterized specimen, the cutoff for true bladder infection should be ≥100 colonies/mL. The cutoff of ≥100,000 colonies/mLis applicable only for clean-catch specimens obtained from asymptomatic patients.
• Clinical laboratories should embrace the new cutoff and report even seemingly low colony counts when the urine sample has been obtained by catheterization.

In preterm labor, amniotic fluid infection without inflammation does not necessarily predict a poor fetal outcome

Combs CA, Gravett M, Garite TJ, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;210(2):125.e1–e15.

In this very important clinical investigation, Combs and colleagues collected amniotic fluid from 305 women with preterm labor. They then measured the amniotic fluid concentration of interleukin-6 (IL-6) and assessed for the presence of microbial invasion of the amniotic cavity (MIAC) by either culture or detection of microbial 16S ribosomal DNA. Based on these test results, investigators divided the patients into five groups:

• Infection—defined as positive MIAC and IL-6 >11.3 ng/mL
• Severe inflammation—negative MIAC and IL-6 >11.3 ng/mL
• Mild inflammation—no MIAC and IL-6 from 2.6 to 11.2 ng/mL
• Colonization—positive MIAC and IL-6 <2.6 ng/mL
• Negative—no MIAC and IL-6 <2.6 ng/mL.

The end points of the investigation were latency period and composite perinatal morbidity and mortality. Perinatal morbidity included respiratory distress syndrome, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, and culture-proven neonatal sepsis.

Related article: Does treating asymptomatic bacterial vaginosis reduce preterm delivery? Hyagriv N. Simhan, MD, MSCR (Examining the Evidence; April 2008)

Interestingly, the infection and severe inflammation groups had similar short latency periods (median of <1 and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively).

The colonization and negative groups also had similar latency periods (median of 23.5 and 25 days, respectively) and similar rates of composite morbidity and mortality (21% and 25%, respectively).

The mild inflammation group had intermediate outcomes.

When Combs and colleagues used multivariate analysis to adjust for gestational age at enrollment, amniotic fluid IL-6 concentrations greater than 11.3 ng/mL and in the range of 2.6 to 11.3 ng/mL—but not MIAC—were associated with increased composite perinatal morbidity and mortality.

What this EVIDENCE means for practiceThis study offers several critically important take-home messages:
• Bacterial colonization of the amniotic fluid, without actual inflammation, is not necessarily associated with an ominous outcome for the fetus
• Varying degrees of inflammation exist
• The more intense the inflammation, the worse the outcome for the baby
• The logical clinical application of this investigation is to modify our practice so that, when we perform an amniocentesis for patients with preterm labor, we look not only for bacterial growth but for the presence of key inflammatory mediators in the amniotic fluid, such as IL-6
• A rapidly available, inexpensive, and easy-to-perform assay for IL-6 would be invaluable in improving our ability to assess patients for subclinical infection and inflammation
• An important question, of course, is whether early implementation of specific anti-inflammatory therapy could alter the prognosis for the fetus in selected cases.

WE WANT TO HEAR FROM YOU! Share your thoughts on this article. Send your Letter to the Editor to: [email protected]

More than 300 attendees heard Dr. Mickey Karram address urodynamics and cystoscopy at the annual Pelvic Anatomy and Gynecologic Surgery Symposium (PAGS) in Las Vegas, December 12-14, 2013. Here, a key topic from his presentation.

Dr. Karram is  Professor of OB/GYN and Urology, University of Cincinnati School of Medicine, and Director, Urogynecology, The Christ Hospital, Cincinnati, Ohio. He also is Course Director of the Pelvic Anatomy and Gynecologic Surgery Symposium (PAGS) and the Female Urology and Urogynecology Symposium (FUUS), both co-sponsored by OBG Management.

FUUS 2014: June 14-16, Aria, Las Vegas
Click here for more info.

More than 300 attendees heard Dr. Mickey Karram address urodynamics and cystoscopy at the annual Pelvic Anatomy and Gynecologic Surgery Symposium (PAGS) in Las Vegas, December 12-14, 2013. Here, a key topic from his presentation.

Dr. Karram is  Professor of OB/GYN and Urology, University of Cincinnati School of Medicine, and Director, Urogynecology, The Christ Hospital, Cincinnati, Ohio. He also is Course Director of the Pelvic Anatomy and Gynecologic Surgery Symposium (PAGS) and the Female Urology and Urogynecology Symposium (FUUS), both co-sponsored by OBG Management.

FUUS 2014: June 14-16, Aria, Las Vegas
Click here for more info.

More than 300 attendees heard Dr. Mickey Karram address urodynamics and cystoscopy at the annual Pelvic Anatomy and Gynecologic Surgery Symposium (PAGS) in Las Vegas, December 12-14, 2013. Here, a key topic from his presentation.

Dr. Karram is  Professor of OB/GYN and Urology, University of Cincinnati School of Medicine, and Director, Urogynecology, The Christ Hospital, Cincinnati, Ohio. He also is Course Director of the Pelvic Anatomy and Gynecologic Surgery Symposium (PAGS) and the Female Urology and Urogynecology Symposium (FUUS), both co-sponsored by OBG Management.

FUUS 2014: June 14-16, Aria, Las Vegas
Click here for more info.