OBG Management

“IN WHICH CLINICAL SITUATIONS CAN THE USE OF THE 52-MG LEVONORGESTREL-RELEASING IUD (MIRENA) AND THE TCU380A COPPER-IUD (PARAGARD) BE EXTENDED?”

ROBERT L. BARBIERI, MD (SEPTEMBER 2016)

Extended-use IUDs and infection risk

For some time now I have been leaving hormonal intrauterine devices (IUDs) in place for 6 to 7 years, until menses returns. In my practice, long-term use of copper-IUDs has been associated with the presence of actinomycosis in the endometrial cavity, although usually without sepsis.

George Haber, MD
Montreal, Canada
 

Suppressing menses, pain with an IUD

I have a number of patients using the 52-mg levonorgestrel-releasing (LNG) IUD (Mirena) for noncontraceptive reasons, especially for reduction or elimination of menstrual flow and/or pain. Many have permanent sterilization in place (tubal sterilization, partner vasectomy) and I tell them we can leave the IUD in as long as they are satisfied with the results, since we are not concerned with pregnancy. Several have continued IUD use well past the 5-year mark.

Alan Smith, MD
Savannah, Georgia
 

LNG-IUD effective for multiple uses

In our practice, we have used the LNG-IUD Mirena off label for over a decade successfully for men-strual suppression in perimenopausal and postmenopausal women effectively for up to 8 years. We often place this device in the uterus after an endometrial ablation. We also offer it extended use as an alternative for menopausal hormone therapy when a progestin is indicated due to the presence of a uterus. Progestin delivery by this IUD is maximized in the endometrium and minimized in the breast and other systemic sites.

John Lenihan Jr, MD
Tacoma, Washington

Dr. Barbieri responds

I thank Dr. Haber for his observations. He notes that users of IUDs may have Actinomyces organisms identified on cervical cytology. These women should be informed of the finding and examined for evidence of active pelvic infection. If the women are asympto-matic and have a normal physical exam, the IUD does not need to be removed and antibiotic treatment is not recommended. If the woman has evidence of pelvic infection, the IUD should be removed and sent for anaerobic culture.

I appreciate that Drs. Smith and Lenihan shared their clinical pearls with readers. Dr. Smith notes that when an LNG-IUD is used to control bleeding in women who are sterilized, there are few concerns about the duration of its contraceptive efficacy, and adequate control of bleeding is a clinically useful end point demonstrating the IUD’s continued efficacy. If bleeding begins to increase after 5 years, the clinician might choose to remove the old device and replace it with a new one. Dr. Lenihan reports his use of the 52-mg LNG-IUD as the progestin in a regimen of menopausal hormone therapy. Of note, there are multiple reports from Finland that use of an LNG-IUD in premenopausal and menopausal women may be associated with an increased risk of breast cancer.^1,2 Conflicting reports from Finland and Germany did not detect an increased risk of breast cancer in women who used an LNG-IUD.^3,4 Clinicians should be aware that when Mirena is used past its approved 5-year time limit, it is an off-label use of the device.

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

“IN WHICH CLINICAL SITUATIONS CAN THE USE OF THE 52-MG LEVONORGESTREL-RELEASING IUD (MIRENA) AND THE TCU380A COPPER-IUD (PARAGARD) BE EXTENDED?”

ROBERT L. BARBIERI, MD (SEPTEMBER 2016)

Extended-use IUDs and infection risk

For some time now I have been leaving hormonal intrauterine devices (IUDs) in place for 6 to 7 years, until menses returns. In my practice, long-term use of copper-IUDs has been associated with the presence of actinomycosis in the endometrial cavity, although usually without sepsis.

George Haber, MD
Montreal, Canada
 

Suppressing menses, pain with an IUD

I have a number of patients using the 52-mg levonorgestrel-releasing (LNG) IUD (Mirena) for noncontraceptive reasons, especially for reduction or elimination of menstrual flow and/or pain. Many have permanent sterilization in place (tubal sterilization, partner vasectomy) and I tell them we can leave the IUD in as long as they are satisfied with the results, since we are not concerned with pregnancy. Several have continued IUD use well past the 5-year mark.

Alan Smith, MD
Savannah, Georgia
 

LNG-IUD effective for multiple uses

In our practice, we have used the LNG-IUD Mirena off label for over a decade successfully for men-strual suppression in perimenopausal and postmenopausal women effectively for up to 8 years. We often place this device in the uterus after an endometrial ablation. We also offer it extended use as an alternative for menopausal hormone therapy when a progestin is indicated due to the presence of a uterus. Progestin delivery by this IUD is maximized in the endometrium and minimized in the breast and other systemic sites.

John Lenihan Jr, MD
Tacoma, Washington

Dr. Barbieri responds

I thank Dr. Haber for his observations. He notes that users of IUDs may have Actinomyces organisms identified on cervical cytology. These women should be informed of the finding and examined for evidence of active pelvic infection. If the women are asympto-matic and have a normal physical exam, the IUD does not need to be removed and antibiotic treatment is not recommended. If the woman has evidence of pelvic infection, the IUD should be removed and sent for anaerobic culture.

I appreciate that Drs. Smith and Lenihan shared their clinical pearls with readers. Dr. Smith notes that when an LNG-IUD is used to control bleeding in women who are sterilized, there are few concerns about the duration of its contraceptive efficacy, and adequate control of bleeding is a clinically useful end point demonstrating the IUD’s continued efficacy. If bleeding begins to increase after 5 years, the clinician might choose to remove the old device and replace it with a new one. Dr. Lenihan reports his use of the 52-mg LNG-IUD as the progestin in a regimen of menopausal hormone therapy. Of note, there are multiple reports from Finland that use of an LNG-IUD in premenopausal and menopausal women may be associated with an increased risk of breast cancer.^1,2 Conflicting reports from Finland and Germany did not detect an increased risk of breast cancer in women who used an LNG-IUD.^3,4 Clinicians should be aware that when Mirena is used past its approved 5-year time limit, it is an off-label use of the device.

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

“IN WHICH CLINICAL SITUATIONS CAN THE USE OF THE 52-MG LEVONORGESTREL-RELEASING IUD (MIRENA) AND THE TCU380A COPPER-IUD (PARAGARD) BE EXTENDED?”

ROBERT L. BARBIERI, MD (SEPTEMBER 2016)

Extended-use IUDs and infection risk

For some time now I have been leaving hormonal intrauterine devices (IUDs) in place for 6 to 7 years, until menses returns. In my practice, long-term use of copper-IUDs has been associated with the presence of actinomycosis in the endometrial cavity, although usually without sepsis.

George Haber, MD
Montreal, Canada
 

Suppressing menses, pain with an IUD

I have a number of patients using the 52-mg levonorgestrel-releasing (LNG) IUD (Mirena) for noncontraceptive reasons, especially for reduction or elimination of menstrual flow and/or pain. Many have permanent sterilization in place (tubal sterilization, partner vasectomy) and I tell them we can leave the IUD in as long as they are satisfied with the results, since we are not concerned with pregnancy. Several have continued IUD use well past the 5-year mark.

Alan Smith, MD
Savannah, Georgia
 

LNG-IUD effective for multiple uses

In our practice, we have used the LNG-IUD Mirena off label for over a decade successfully for men-strual suppression in perimenopausal and postmenopausal women effectively for up to 8 years. We often place this device in the uterus after an endometrial ablation. We also offer it extended use as an alternative for menopausal hormone therapy when a progestin is indicated due to the presence of a uterus. Progestin delivery by this IUD is maximized in the endometrium and minimized in the breast and other systemic sites.

John Lenihan Jr, MD
Tacoma, Washington

Dr. Barbieri responds

I thank Dr. Haber for his observations. He notes that users of IUDs may have Actinomyces organisms identified on cervical cytology. These women should be informed of the finding and examined for evidence of active pelvic infection. If the women are asympto-matic and have a normal physical exam, the IUD does not need to be removed and antibiotic treatment is not recommended. If the woman has evidence of pelvic infection, the IUD should be removed and sent for anaerobic culture.

I appreciate that Drs. Smith and Lenihan shared their clinical pearls with readers. Dr. Smith notes that when an LNG-IUD is used to control bleeding in women who are sterilized, there are few concerns about the duration of its contraceptive efficacy, and adequate control of bleeding is a clinically useful end point demonstrating the IUD’s continued efficacy. If bleeding begins to increase after 5 years, the clinician might choose to remove the old device and replace it with a new one. Dr. Lenihan reports his use of the 52-mg LNG-IUD as the progestin in a regimen of menopausal hormone therapy. Of note, there are multiple reports from Finland that use of an LNG-IUD in premenopausal and menopausal women may be associated with an increased risk of breast cancer.^1,2 Conflicting reports from Finland and Germany did not detect an increased risk of breast cancer in women who used an LNG-IUD.^3,4 Clinicians should be aware that when Mirena is used past its approved 5-year time limit, it is an off-label use of the device.

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

Cesarean delivery is now the most commonly performed major operation in hospitals across the United States. Approximately 30% of the 4 million deliveries that occur each year are by cesarean. Endometritis and wound infection (superficial and deep surgical site infection) are the most common postoperative complications of cesarean delivery. These 2 infections usually can be treated in a straightforward manner with antibiotics or surgical drainage. In some cases, however, they can lead to serious sequelae, such as pelvic abscess, septic pelvic vein thrombophlebitis, and wound dehiscence/evisceration, thereby prolonging the patient’s hospitalization and significantly increasing medical expenses.

Accordingly, in the past 50 years many investigators have proposed various specific measures to reduce the risk of postcesarean infection. In this article, we critically evaluate 2 of these major interventions: methods of skin preparation and administration of prophylactic antibiotics. In part 2 of this series next month, we will review the evidence regarding preoperative bathing with an antiseptic, preoperative vaginal cleansing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.

CASE Cesarean delivery required for nonprogressing labor

A 26-year-old obese primigravid woman, body mass index (BMI) 37 kg m², at 40 weeks’ gestation has been in labor for 20 hours. Her membranes have been ruptured for 16 hours. Her cervix is completely effaced and is 7 cm dilated. The fetal head is at −1 cm station. Her cervical examination findings have not changed in 4 hours despite adequate uterine contractility documented by intrauterine pressure catheter. You are now ready to proceed with cesarean delivery, and you want to do everything possible to prevent the patient from developing a postoperative infection.

What are the best practices for postcesarean infection prevention in this patient?

Skin preparation

Adequate preoperative skin preparation is an important first step in preventing post‑ cesarean infection.

How should you prepare the patient’s skin for surgery?

Two issues to address when preparing the abdominal wall for surgery are hair removal and skin cleansing. More than 40 years ago, Cruse and Foord definitively answered the question about hair removal.¹ In a landmark cohort investigation of more than 23,000 patients having many different types of operative procedures, they demonstrated that shaving the hair on the evening before surgery resulted in a higher rate of wound infection than clipping the hair, removing the hair with a depilatory cream just before surgery, or not removing the hair at all.

Three recent investigations have thoughtfully addressed the issue of skin cleansing. Darouiche and colleagues conducted a prospective, randomized, multicenter trial comparing chlorhexidine-alcohol with povidone-iodine for skin preparation before surgery.² Their investigation included 849 patients having many different types of surgical procedures, only a minority of which were in obstetric and gynecologic patients. They demonstrated fewer superficial wound infections in patients in the chlorhexidine-alcohol group (4.2% vs 8.6%, P = .008). Of even greater importance, patients in the chlorhexidine-alcohol group had fewer deep wound infections (1% vs 3%, P = .005).

Ngai and co-workers recently reported the results of a randomized controlled trial (RCT) in which women undergoing nonurgent cesarean delivery had their skin cleansed with povidone-iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions.³ The overall rate of surgical site infection was just 4.3%. The 3 groups had comparable infection rates and, accordingly, the authors were unable to conclude that one type of skin preparation was superior to the other.

The most informative recent investigation was by Tuuli and colleagues, who evaluated 1,147 patients having cesarean delivery assigned to undergo skin preparation with either chlorhexidine-alcohol or iodine-alcohol.⁴ Unlike the study by Ngai and co-workers, in this study approximately 40% of the patients in each treatment arm had unscheduled, urgent cesarean deliveries.^3,4 Overall, the rate of infection in the chlorhexidine-alcohol group was 4.0% compared with 7.3% in the iodine-alcohol group (relative risk [RR], 0.55; 95% confidence interval [CI], 0.34–0.90, P = .02).

What the evidence says

Based on the evidence cited above, we advise removing hair at the incision site with clippers or depilatory cream just before the start of surgery. The abdomen should then be cleansed with a chlorhexidine-alcohol solution (Level I Evidence, Level 1A Recommendation; TABLE).

Antibiotic prophylaxis

Questions to consider regarding antibiotic prophylaxis for cesarean delivery include appropriateness of treatment, antibiotic(s) selection, timing of administration, dose, and special circumstances.

Should you give the patient prophylactic antibiotics?

Prophylactic antibiotics are justified for surgical procedures whenever 3 major criteria are met⁵:

1. the surgical site is inevitably contaminated with bacteria
2. in the absence of prophylaxis, the frequency of infection at the operative site is unacceptably high
3. operative site infections have the potential to lead to serious, potentially life-threatening sequelae.

Without a doubt, all 3 of these criteria are fulfilled when considering either urgent or nonurgent cesarean delivery. When cesarean delivery follows a long labor complicated by ruptured membranes, multiple internal vaginal examinations, and internal fetal monitoring, the operative site is inevitably contaminated with hundreds of thousands of pathogenic bacteria. Even when cesarean delivery is scheduled to occur before the onset of labor and ruptured membranes, a high concentration of vaginal organisms is introduced into the uterine and pelvic cavities coincident with making the hysterotomy incision.⁶

In the era before prophylactic antibiotics were used routinely, postoperative infection rates in some highly indigent patient populations approached 85%.⁵ Finally, as noted previously, postcesarean endometritis may progress to pelvic abscess formation, septic pelvic vein thrombophlebitis, and septic shock; wound infections may be complicated by dehiscence and evisceration.

When should you administer antibiotics: Before the surgical incision or after cord clamping?

More than 50 years ago, Burke conducted the classic sequence of basic science experiments that forms the foundation for use of prophylactic antibiotics.⁷ Using a guinea pig model, he showed that prophylactic antibiotics exert their most pronounced effect when they are administered before the surgical incision is made and before bacterial contamination occurs. Prophylaxis that is delayed more than 4 hours after the start of surgery will likely be ineffective.

Interestingly, however, when clinicians first began using prophylactic antibiotics for cesarean delivery, some investigators expressed concern about the possible exposure of the neonate to antibiotics just before delivery—specifically, whether this exposure would increase the frequency of evaluations for suspected sepsis or would promote resistance among organisms that would make neonatal sepsis more difficult to treat.

Gordon and colleagues published an important report in 1979 that showed that preoperative administration of ampicillin did not increase the frequency of immediate or delayed neonatal infections.⁸ However, delaying the administration of ampicillin until after the umbilical cord was clamped was just as effective in preventing post‑cesarean endometritis. Subsequently, Cunningham and co-workers showed that preoperative administration of prophylactic antibiotics significantly increased the frequency of sepsis workups in exposed neonates compared with infants with no preoperative antibiotic exposure (28% vs 15%; P<.025).⁹ Based on these 2 reports, obstetricians adopted a policy of delaying antibiotic administration until after the infant’s umbilical cord was clamped.

In 2007, Sullivan and colleagues challenged this long-standing practice.¹⁰ In a carefully designed prospective, randomized, double-blind trial, they showed that patients who received preoperative cefazolin had a significant reduction in the frequency of endometritis compared with women who received the same antibiotic after cord clamping (1% vs 5%; RR, 0.2; 95% CI, 0.2–0.94). The rate of wound infection was lower in the preoperative antibiotic group (3% vs 5%), but this difference did not reach statistical significance. The total infection-related morbidity was significantly reduced in women who received antibiotics preoperatively (4.0% vs 11.5%; RR, 0.4; 95% CI, 0.18–0.87). Additionally, there was no increase in the frequency of proven or suspected neonatal infection in the infants exposed to antibiotics before delivery.

Subsequent to the publication by Sullivan and colleagues, other reports have confirmed that administration of antibiotics prior to surgery is superior to administration after clamping of the umbilical cord.^10–12 Thus, we have come full circle back to Burke’s principle established more than a half century ago.⁷

Which antibiotic(s) should you administer for prophylaxis, and how many doses?

In an earlier review, one of us (PD) examined the evidence regarding choice of antibiotics and number of doses, concluding that a single dose of a first-generation cephalosporin, such as cefazolin, was the preferred regimen.⁵ The single dose was comparable in effectiveness to 2- or 3-dose regimens and to single- or multiple-dose regimens of broader-spectrum agents. For more than 20 years now, the standard of care for antibiotic prophylaxis has been a single 1- to 2-g dose of cefazolin.

Several recent reports, however, have raised the question of whether the prophylactic effect could be enhanced if the spectrum of activity of the antibiotic regimen was broadened to include an agent effective against Ureaplasma species.

Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection; they showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis.¹³ In a follow-up report from the same institution, Tita and co-workers demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.¹⁴ In both of these investigations, the antibiotics were administered after cord clamping.

In a subsequent report, Ward and Duff¹⁵ showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a very low rate of both endometritis and wound infection in a population similar to that studied by Tita et al.^13,14

Very recently, Tita and associates published the results of the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial conducted at 14 US hospitals.¹⁶ This study included 2,013 women undergoing cesarean delivery during labor or after membrane rupture who were randomly assigned to receive intravenous azithromycin 500 mg (n = 1,019) or placebo (n = 994). All women also received standard antibiotic prophylaxis with cefazolin. The primary outcome (a composite of endometritis, wound infection, or other infection within 6 weeks) was significantly lower in the azithromycin group than in the placebo group (6.1% vs 12.0%, P<.001). In addition, there were significant differences between the treatment groups in the rates of endometritis (3.8% in the azithromycin group vs 6.1% in the placebo group, P = .02) as well as in the rates of wound infection (2.4% vs 6.6%, respectively, P<.001). Of additional note, there were no differences between the 2 groups in the composite neonatal outcome of death and serious neonatal complications (14.3% vs 13.6%, P = .63).The investigators concluded that extended-spectrum prophylaxis with adjunctive azithromycin safely reduces infection rates without raising the risk of neonatal adverse outcomes.

What the evidence says

We conclude that all patients, even those having a scheduled cesarean before the onset of labor or ruptured membranes, should receive prophylactic antibiotics in a single dose administered preoperatively rather than after cord clamping (Level I Evidence, Level 1A Recommendation; TABLE). In high-risk populations (eg, women in labor with ruptured membranes who are having an urgent cesarean), for whom the baseline risk of infection is high, administer the combination of cefazolin plus azithromycin in lieu of cefazolin alone (Level I Evidence, Level 1A Recommendation; TABLE).

If the patient has a history of an immediate hypersensitivity reaction to beta-lactam antibiotics, we recommend the combination of clindamycin (900 mg) plus gentamicin (1.5 mg/kg) as a single infusion prior to surgery. We base this recommendation on the need to provide reasonable coverage against a broad range of pathogens. Clindamycin covers gram-positive aerobes, such as staphylococci species and group B streptococci, and anaerobes; gentamicin covers aerobic gram-negative bacilli. A single agent, such as clindamycin or metronidazole, does not provide the broad-based coverage necessary for effective prophylaxis (Level III Evidence, Level 1C Recommendation; TABLE).

If the patient is overweight or obese, should you modify the antibiotic dose?

The prevalence of obesity in the United States continues to increase. One-third of all US reproductive-aged women are obese, and 6% of women are extremely obese.¹⁷ Obesity increases the risk of postcesarean infection 3- to 5- fold.¹⁸ Because both pregnancy and obesity increase the total volume of a drug’s distribution, achieving adequate antibiotic tissue concentrations may be hindered by a dilutional effect. Furthermore, pharmacokinetic studies consistently have shown that the tissue concentration of an antibiotic—which, ideally, should be above the minimum inhibitory concentration (MIC) for common bacteria—determines the susceptibility of those tissues to infection, regardless of whether the serum concentration of the antibiotic is in the therapeutic range.¹⁹

These concerns have led to several recent investigations evaluating different doses of cefazolin for obese patients. Pevzner and colleagues conducted a prospective cohort study of 29 women having a scheduled cesarean delivery.²⁰ The patients were divided into 3 groups: lean (BMI <30 kg m²), obese (BMI 30.0–39.9 kg m²), and extremely obese (BMI >40 kg m²). All women received a 2-g dose of cefazolin 30 to 60 minutes before surgery. Cefazolin concentrations in adipose tissue obtained at the time of skin incision were inversely proportional to maternal BMI (r, −0.67; P<.001). All specimens demonstrated a therapeutic concentration (>1 µg/g) of cefazolin for gram-positive cocci, but 20% of the obese women and 33% of the extremely obese women did not achieve the MIC (>4 µg/g) for gram-negative bacilli (P = .29 and P = .14, respectively). At the time of skin closure, 20% of obese women and 44% of extremely obese women did not have tissue concentrations that exceeded the MIC for gram-negative bacteria.

Swank and associates conducted a prospective cohort study that included 28 women.¹⁸ They demonstrated that, after a 2-g dose of cefazolin, only 20% of the obese women (BMI 30–40 kg m²) and 0% of the extremely obese women (BMI >40 kg m²) achieved an adipose tissue concentration that exceeded the MIC for gram-negative rods (8 µg/mL). However, 100% and 71.4%, respectively, achieved such a tissue concentration after a 3-g dose. When the women were stratified by actual weight, there was a statistically significant difference between those who weighed less than 120 kg and those who weighed more than 120 kg. Seventy-nine percent of the former had a tissue concentration of cefazolin greater than 8 µg/mL compared with 0% of the women who weighed more than 120 kg. Based on these observations, the authors recommended a 3-g dose of cefazolin for women who weigh more than 120 kg.

In a double-blind RCT with 26 obese women (BMI ≥30 kg m²), Young and colleagues demonstrated that, at the time of hysterotomy and fascial closure, significantly higher concentrations of cefazolin were found in the adipose tissue of obese women who received a 3-g dose of antibiotic compared with those who received a 2-g dose.²¹ However, all concentrations of cefazolin were consistently above the MIC of cefazolin for gram-positive cocci (1 µg/g) and gram-negative bacilli (4 µg/g). Further, Maggio and co-workers conducted a double-blind RCT comparing a 2-g dose of cefazolin versus a 3-g dose in 57 obese women (BMI ≥30 kg m²).²² They found no statistically significant difference in the percentage of women who had tissue concentrations of cefazolin greater than the MIC for gram-positive cocci (8 µg/g). All samples were above the MIC of cefazolin for gram-negative bacilli (2 µg/g). Based on these data, these investigators did not recommend increasing the dose of cefazolin from 2 g to 3 g in obese patients.^21,22

The studies discussed above are difficult to compare for 3 reasons. First, each study used a different MIC of cefazolin for both gram-positive and gram-negative bacteria. Second, the authors sampled different maternal tissues or serum at varying times during the cesarean delivery. Third, the studies did not specifically investigate, or were not powered sufficiently to address, the more important clinical outcome of surgical site infection. In a recent historical cohort study, Ward and Duff were unable to show that increasing the dose of cefazolin to 2 g in all women with a BMI <30 kg m² and to 3 g in all women with a BMI >30 kg m² reduced the rate of endometritis and wound infection below the level already achieved with combined prophylaxis with cefazolin (1 g) plus azithromycin (500 mg).¹⁵

Sutton and colleagues recently assessed the pharmacokinetics of azithromycin when used as prophylaxis for cesarean delivery.²³ They studied 30 women who had a scheduled cesarean delivery and who received a 500-mg intravenous dose of azithromycin that was initiated 15, 30, or 60 minutes before the surgical incision and then infused over 1 hour. They obtained maternal plasma samples multiple times during the first 8 hours after surgery. They also obtained samples of amniotic fluid, placenta, myometrium, adipose tissue, and umbilical cord blood intraoperatively. The median concentration of azithromycin in adipose tissue was 102 ng/g, which is below the MIC₅₀ for Ureaplasma species (250 ng/mL). The median concentration in myometrial tissue was 402 ng/g. The concentration in maternal plasma consistently exceeded the MIC₅₀ for Ureaplasma species.

What the evidence says

All women, regardless of weight, who will undergo cesarean delivery should receive a 2-g dose of cefazolin (Level II Evidence, Level 1B Recommendation; TABLE).If azithromycin is used in combination with cefazolin, an intravenous dose of 500 mg appears to provide adequate concentrations in serum and myometrium, but probably not in adipose tissue. More information is needed before we can make a firm recommendation about weight-based dosing of azithromycin.

CASE Resolved

For the 26-year-old obese laboring patient about to undergo cesarean delivery, reasonable steps for prevention of infection include removing the hair at the incision site with clippers or depilatory cream immediately prior to the start of surgery; cleansing the abdomen with a chlorhexidine-alcohol solution; and administering cefazolin (2 g) plus azithromycin (500 mg) preoperatively.

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

Cesarean delivery is now the most commonly performed major operation in hospitals across the United States. Approximately 30% of the 4 million deliveries that occur each year are by cesarean. Endometritis and wound infection (superficial and deep surgical site infection) are the most common postoperative complications of cesarean delivery. These 2 infections usually can be treated in a straightforward manner with antibiotics or surgical drainage. In some cases, however, they can lead to serious sequelae, such as pelvic abscess, septic pelvic vein thrombophlebitis, and wound dehiscence/evisceration, thereby prolonging the patient’s hospitalization and significantly increasing medical expenses.

Accordingly, in the past 50 years many investigators have proposed various specific measures to reduce the risk of postcesarean infection. In this article, we critically evaluate 2 of these major interventions: methods of skin preparation and administration of prophylactic antibiotics. In part 2 of this series next month, we will review the evidence regarding preoperative bathing with an antiseptic, preoperative vaginal cleansing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.

CASE Cesarean delivery required for nonprogressing labor

A 26-year-old obese primigravid woman, body mass index (BMI) 37 kg m², at 40 weeks’ gestation has been in labor for 20 hours. Her membranes have been ruptured for 16 hours. Her cervix is completely effaced and is 7 cm dilated. The fetal head is at −1 cm station. Her cervical examination findings have not changed in 4 hours despite adequate uterine contractility documented by intrauterine pressure catheter. You are now ready to proceed with cesarean delivery, and you want to do everything possible to prevent the patient from developing a postoperative infection.

What are the best practices for postcesarean infection prevention in this patient?

Skin preparation

Adequate preoperative skin preparation is an important first step in preventing post‑ cesarean infection.

How should you prepare the patient’s skin for surgery?

Two issues to address when preparing the abdominal wall for surgery are hair removal and skin cleansing. More than 40 years ago, Cruse and Foord definitively answered the question about hair removal.¹ In a landmark cohort investigation of more than 23,000 patients having many different types of operative procedures, they demonstrated that shaving the hair on the evening before surgery resulted in a higher rate of wound infection than clipping the hair, removing the hair with a depilatory cream just before surgery, or not removing the hair at all.

Three recent investigations have thoughtfully addressed the issue of skin cleansing. Darouiche and colleagues conducted a prospective, randomized, multicenter trial comparing chlorhexidine-alcohol with povidone-iodine for skin preparation before surgery.² Their investigation included 849 patients having many different types of surgical procedures, only a minority of which were in obstetric and gynecologic patients. They demonstrated fewer superficial wound infections in patients in the chlorhexidine-alcohol group (4.2% vs 8.6%, P = .008). Of even greater importance, patients in the chlorhexidine-alcohol group had fewer deep wound infections (1% vs 3%, P = .005).

Ngai and co-workers recently reported the results of a randomized controlled trial (RCT) in which women undergoing nonurgent cesarean delivery had their skin cleansed with povidone-iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions.³ The overall rate of surgical site infection was just 4.3%. The 3 groups had comparable infection rates and, accordingly, the authors were unable to conclude that one type of skin preparation was superior to the other.

The most informative recent investigation was by Tuuli and colleagues, who evaluated 1,147 patients having cesarean delivery assigned to undergo skin preparation with either chlorhexidine-alcohol or iodine-alcohol.⁴ Unlike the study by Ngai and co-workers, in this study approximately 40% of the patients in each treatment arm had unscheduled, urgent cesarean deliveries.^3,4 Overall, the rate of infection in the chlorhexidine-alcohol group was 4.0% compared with 7.3% in the iodine-alcohol group (relative risk [RR], 0.55; 95% confidence interval [CI], 0.34–0.90, P = .02).

What the evidence says

Based on the evidence cited above, we advise removing hair at the incision site with clippers or depilatory cream just before the start of surgery. The abdomen should then be cleansed with a chlorhexidine-alcohol solution (Level I Evidence, Level 1A Recommendation; TABLE).

Antibiotic prophylaxis

Questions to consider regarding antibiotic prophylaxis for cesarean delivery include appropriateness of treatment, antibiotic(s) selection, timing of administration, dose, and special circumstances.

Should you give the patient prophylactic antibiotics?

Prophylactic antibiotics are justified for surgical procedures whenever 3 major criteria are met⁵:

1. the surgical site is inevitably contaminated with bacteria
2. in the absence of prophylaxis, the frequency of infection at the operative site is unacceptably high
3. operative site infections have the potential to lead to serious, potentially life-threatening sequelae.

Without a doubt, all 3 of these criteria are fulfilled when considering either urgent or nonurgent cesarean delivery. When cesarean delivery follows a long labor complicated by ruptured membranes, multiple internal vaginal examinations, and internal fetal monitoring, the operative site is inevitably contaminated with hundreds of thousands of pathogenic bacteria. Even when cesarean delivery is scheduled to occur before the onset of labor and ruptured membranes, a high concentration of vaginal organisms is introduced into the uterine and pelvic cavities coincident with making the hysterotomy incision.⁶

In the era before prophylactic antibiotics were used routinely, postoperative infection rates in some highly indigent patient populations approached 85%.⁵ Finally, as noted previously, postcesarean endometritis may progress to pelvic abscess formation, septic pelvic vein thrombophlebitis, and septic shock; wound infections may be complicated by dehiscence and evisceration.

When should you administer antibiotics: Before the surgical incision or after cord clamping?

More than 50 years ago, Burke conducted the classic sequence of basic science experiments that forms the foundation for use of prophylactic antibiotics.⁷ Using a guinea pig model, he showed that prophylactic antibiotics exert their most pronounced effect when they are administered before the surgical incision is made and before bacterial contamination occurs. Prophylaxis that is delayed more than 4 hours after the start of surgery will likely be ineffective.

Interestingly, however, when clinicians first began using prophylactic antibiotics for cesarean delivery, some investigators expressed concern about the possible exposure of the neonate to antibiotics just before delivery—specifically, whether this exposure would increase the frequency of evaluations for suspected sepsis or would promote resistance among organisms that would make neonatal sepsis more difficult to treat.

Gordon and colleagues published an important report in 1979 that showed that preoperative administration of ampicillin did not increase the frequency of immediate or delayed neonatal infections.⁸ However, delaying the administration of ampicillin until after the umbilical cord was clamped was just as effective in preventing post‑cesarean endometritis. Subsequently, Cunningham and co-workers showed that preoperative administration of prophylactic antibiotics significantly increased the frequency of sepsis workups in exposed neonates compared with infants with no preoperative antibiotic exposure (28% vs 15%; P<.025).⁹ Based on these 2 reports, obstetricians adopted a policy of delaying antibiotic administration until after the infant’s umbilical cord was clamped.

In 2007, Sullivan and colleagues challenged this long-standing practice.¹⁰ In a carefully designed prospective, randomized, double-blind trial, they showed that patients who received preoperative cefazolin had a significant reduction in the frequency of endometritis compared with women who received the same antibiotic after cord clamping (1% vs 5%; RR, 0.2; 95% CI, 0.2–0.94). The rate of wound infection was lower in the preoperative antibiotic group (3% vs 5%), but this difference did not reach statistical significance. The total infection-related morbidity was significantly reduced in women who received antibiotics preoperatively (4.0% vs 11.5%; RR, 0.4; 95% CI, 0.18–0.87). Additionally, there was no increase in the frequency of proven or suspected neonatal infection in the infants exposed to antibiotics before delivery.

Subsequent to the publication by Sullivan and colleagues, other reports have confirmed that administration of antibiotics prior to surgery is superior to administration after clamping of the umbilical cord.^10–12 Thus, we have come full circle back to Burke’s principle established more than a half century ago.⁷

Which antibiotic(s) should you administer for prophylaxis, and how many doses?

In an earlier review, one of us (PD) examined the evidence regarding choice of antibiotics and number of doses, concluding that a single dose of a first-generation cephalosporin, such as cefazolin, was the preferred regimen.⁵ The single dose was comparable in effectiveness to 2- or 3-dose regimens and to single- or multiple-dose regimens of broader-spectrum agents. For more than 20 years now, the standard of care for antibiotic prophylaxis has been a single 1- to 2-g dose of cefazolin.

Several recent reports, however, have raised the question of whether the prophylactic effect could be enhanced if the spectrum of activity of the antibiotic regimen was broadened to include an agent effective against Ureaplasma species.

Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection; they showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis.¹³ In a follow-up report from the same institution, Tita and co-workers demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.¹⁴ In both of these investigations, the antibiotics were administered after cord clamping.

In a subsequent report, Ward and Duff¹⁵ showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a very low rate of both endometritis and wound infection in a population similar to that studied by Tita et al.^13,14

Very recently, Tita and associates published the results of the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial conducted at 14 US hospitals.¹⁶ This study included 2,013 women undergoing cesarean delivery during labor or after membrane rupture who were randomly assigned to receive intravenous azithromycin 500 mg (n = 1,019) or placebo (n = 994). All women also received standard antibiotic prophylaxis with cefazolin. The primary outcome (a composite of endometritis, wound infection, or other infection within 6 weeks) was significantly lower in the azithromycin group than in the placebo group (6.1% vs 12.0%, P<.001). In addition, there were significant differences between the treatment groups in the rates of endometritis (3.8% in the azithromycin group vs 6.1% in the placebo group, P = .02) as well as in the rates of wound infection (2.4% vs 6.6%, respectively, P<.001). Of additional note, there were no differences between the 2 groups in the composite neonatal outcome of death and serious neonatal complications (14.3% vs 13.6%, P = .63).The investigators concluded that extended-spectrum prophylaxis with adjunctive azithromycin safely reduces infection rates without raising the risk of neonatal adverse outcomes.

What the evidence says

We conclude that all patients, even those having a scheduled cesarean before the onset of labor or ruptured membranes, should receive prophylactic antibiotics in a single dose administered preoperatively rather than after cord clamping (Level I Evidence, Level 1A Recommendation; TABLE). In high-risk populations (eg, women in labor with ruptured membranes who are having an urgent cesarean), for whom the baseline risk of infection is high, administer the combination of cefazolin plus azithromycin in lieu of cefazolin alone (Level I Evidence, Level 1A Recommendation; TABLE).

If the patient has a history of an immediate hypersensitivity reaction to beta-lactam antibiotics, we recommend the combination of clindamycin (900 mg) plus gentamicin (1.5 mg/kg) as a single infusion prior to surgery. We base this recommendation on the need to provide reasonable coverage against a broad range of pathogens. Clindamycin covers gram-positive aerobes, such as staphylococci species and group B streptococci, and anaerobes; gentamicin covers aerobic gram-negative bacilli. A single agent, such as clindamycin or metronidazole, does not provide the broad-based coverage necessary for effective prophylaxis (Level III Evidence, Level 1C Recommendation; TABLE).

If the patient is overweight or obese, should you modify the antibiotic dose?

The prevalence of obesity in the United States continues to increase. One-third of all US reproductive-aged women are obese, and 6% of women are extremely obese.¹⁷ Obesity increases the risk of postcesarean infection 3- to 5- fold.¹⁸ Because both pregnancy and obesity increase the total volume of a drug’s distribution, achieving adequate antibiotic tissue concentrations may be hindered by a dilutional effect. Furthermore, pharmacokinetic studies consistently have shown that the tissue concentration of an antibiotic—which, ideally, should be above the minimum inhibitory concentration (MIC) for common bacteria—determines the susceptibility of those tissues to infection, regardless of whether the serum concentration of the antibiotic is in the therapeutic range.¹⁹

These concerns have led to several recent investigations evaluating different doses of cefazolin for obese patients. Pevzner and colleagues conducted a prospective cohort study of 29 women having a scheduled cesarean delivery.²⁰ The patients were divided into 3 groups: lean (BMI <30 kg m²), obese (BMI 30.0–39.9 kg m²), and extremely obese (BMI >40 kg m²). All women received a 2-g dose of cefazolin 30 to 60 minutes before surgery. Cefazolin concentrations in adipose tissue obtained at the time of skin incision were inversely proportional to maternal BMI (r, −0.67; P<.001). All specimens demonstrated a therapeutic concentration (>1 µg/g) of cefazolin for gram-positive cocci, but 20% of the obese women and 33% of the extremely obese women did not achieve the MIC (>4 µg/g) for gram-negative bacilli (P = .29 and P = .14, respectively). At the time of skin closure, 20% of obese women and 44% of extremely obese women did not have tissue concentrations that exceeded the MIC for gram-negative bacteria.

Swank and associates conducted a prospective cohort study that included 28 women.¹⁸ They demonstrated that, after a 2-g dose of cefazolin, only 20% of the obese women (BMI 30–40 kg m²) and 0% of the extremely obese women (BMI >40 kg m²) achieved an adipose tissue concentration that exceeded the MIC for gram-negative rods (8 µg/mL). However, 100% and 71.4%, respectively, achieved such a tissue concentration after a 3-g dose. When the women were stratified by actual weight, there was a statistically significant difference between those who weighed less than 120 kg and those who weighed more than 120 kg. Seventy-nine percent of the former had a tissue concentration of cefazolin greater than 8 µg/mL compared with 0% of the women who weighed more than 120 kg. Based on these observations, the authors recommended a 3-g dose of cefazolin for women who weigh more than 120 kg.

In a double-blind RCT with 26 obese women (BMI ≥30 kg m²), Young and colleagues demonstrated that, at the time of hysterotomy and fascial closure, significantly higher concentrations of cefazolin were found in the adipose tissue of obese women who received a 3-g dose of antibiotic compared with those who received a 2-g dose.²¹ However, all concentrations of cefazolin were consistently above the MIC of cefazolin for gram-positive cocci (1 µg/g) and gram-negative bacilli (4 µg/g). Further, Maggio and co-workers conducted a double-blind RCT comparing a 2-g dose of cefazolin versus a 3-g dose in 57 obese women (BMI ≥30 kg m²).²² They found no statistically significant difference in the percentage of women who had tissue concentrations of cefazolin greater than the MIC for gram-positive cocci (8 µg/g). All samples were above the MIC of cefazolin for gram-negative bacilli (2 µg/g). Based on these data, these investigators did not recommend increasing the dose of cefazolin from 2 g to 3 g in obese patients.^21,22

The studies discussed above are difficult to compare for 3 reasons. First, each study used a different MIC of cefazolin for both gram-positive and gram-negative bacteria. Second, the authors sampled different maternal tissues or serum at varying times during the cesarean delivery. Third, the studies did not specifically investigate, or were not powered sufficiently to address, the more important clinical outcome of surgical site infection. In a recent historical cohort study, Ward and Duff were unable to show that increasing the dose of cefazolin to 2 g in all women with a BMI <30 kg m² and to 3 g in all women with a BMI >30 kg m² reduced the rate of endometritis and wound infection below the level already achieved with combined prophylaxis with cefazolin (1 g) plus azithromycin (500 mg).¹⁵

Sutton and colleagues recently assessed the pharmacokinetics of azithromycin when used as prophylaxis for cesarean delivery.²³ They studied 30 women who had a scheduled cesarean delivery and who received a 500-mg intravenous dose of azithromycin that was initiated 15, 30, or 60 minutes before the surgical incision and then infused over 1 hour. They obtained maternal plasma samples multiple times during the first 8 hours after surgery. They also obtained samples of amniotic fluid, placenta, myometrium, adipose tissue, and umbilical cord blood intraoperatively. The median concentration of azithromycin in adipose tissue was 102 ng/g, which is below the MIC₅₀ for Ureaplasma species (250 ng/mL). The median concentration in myometrial tissue was 402 ng/g. The concentration in maternal plasma consistently exceeded the MIC₅₀ for Ureaplasma species.

What the evidence says

All women, regardless of weight, who will undergo cesarean delivery should receive a 2-g dose of cefazolin (Level II Evidence, Level 1B Recommendation; TABLE).If azithromycin is used in combination with cefazolin, an intravenous dose of 500 mg appears to provide adequate concentrations in serum and myometrium, but probably not in adipose tissue. More information is needed before we can make a firm recommendation about weight-based dosing of azithromycin.

CASE Resolved

For the 26-year-old obese laboring patient about to undergo cesarean delivery, reasonable steps for prevention of infection include removing the hair at the incision site with clippers or depilatory cream immediately prior to the start of surgery; cleansing the abdomen with a chlorhexidine-alcohol solution; and administering cefazolin (2 g) plus azithromycin (500 mg) preoperatively.

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

Cesarean delivery is now the most commonly performed major operation in hospitals across the United States. Approximately 30% of the 4 million deliveries that occur each year are by cesarean. Endometritis and wound infection (superficial and deep surgical site infection) are the most common postoperative complications of cesarean delivery. These 2 infections usually can be treated in a straightforward manner with antibiotics or surgical drainage. In some cases, however, they can lead to serious sequelae, such as pelvic abscess, septic pelvic vein thrombophlebitis, and wound dehiscence/evisceration, thereby prolonging the patient’s hospitalization and significantly increasing medical expenses.

Accordingly, in the past 50 years many investigators have proposed various specific measures to reduce the risk of postcesarean infection. In this article, we critically evaluate 2 of these major interventions: methods of skin preparation and administration of prophylactic antibiotics. In part 2 of this series next month, we will review the evidence regarding preoperative bathing with an antiseptic, preoperative vaginal cleansing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.

CASE Cesarean delivery required for nonprogressing labor

A 26-year-old obese primigravid woman, body mass index (BMI) 37 kg m², at 40 weeks’ gestation has been in labor for 20 hours. Her membranes have been ruptured for 16 hours. Her cervix is completely effaced and is 7 cm dilated. The fetal head is at −1 cm station. Her cervical examination findings have not changed in 4 hours despite adequate uterine contractility documented by intrauterine pressure catheter. You are now ready to proceed with cesarean delivery, and you want to do everything possible to prevent the patient from developing a postoperative infection.

What are the best practices for postcesarean infection prevention in this patient?

Skin preparation

Adequate preoperative skin preparation is an important first step in preventing post‑ cesarean infection.

How should you prepare the patient’s skin for surgery?

Two issues to address when preparing the abdominal wall for surgery are hair removal and skin cleansing. More than 40 years ago, Cruse and Foord definitively answered the question about hair removal.¹ In a landmark cohort investigation of more than 23,000 patients having many different types of operative procedures, they demonstrated that shaving the hair on the evening before surgery resulted in a higher rate of wound infection than clipping the hair, removing the hair with a depilatory cream just before surgery, or not removing the hair at all.

Three recent investigations have thoughtfully addressed the issue of skin cleansing. Darouiche and colleagues conducted a prospective, randomized, multicenter trial comparing chlorhexidine-alcohol with povidone-iodine for skin preparation before surgery.² Their investigation included 849 patients having many different types of surgical procedures, only a minority of which were in obstetric and gynecologic patients. They demonstrated fewer superficial wound infections in patients in the chlorhexidine-alcohol group (4.2% vs 8.6%, P = .008). Of even greater importance, patients in the chlorhexidine-alcohol group had fewer deep wound infections (1% vs 3%, P = .005).

Ngai and co-workers recently reported the results of a randomized controlled trial (RCT) in which women undergoing nonurgent cesarean delivery had their skin cleansed with povidone-iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions.³ The overall rate of surgical site infection was just 4.3%. The 3 groups had comparable infection rates and, accordingly, the authors were unable to conclude that one type of skin preparation was superior to the other.

The most informative recent investigation was by Tuuli and colleagues, who evaluated 1,147 patients having cesarean delivery assigned to undergo skin preparation with either chlorhexidine-alcohol or iodine-alcohol.⁴ Unlike the study by Ngai and co-workers, in this study approximately 40% of the patients in each treatment arm had unscheduled, urgent cesarean deliveries.^3,4 Overall, the rate of infection in the chlorhexidine-alcohol group was 4.0% compared with 7.3% in the iodine-alcohol group (relative risk [RR], 0.55; 95% confidence interval [CI], 0.34–0.90, P = .02).

What the evidence says

Based on the evidence cited above, we advise removing hair at the incision site with clippers or depilatory cream just before the start of surgery. The abdomen should then be cleansed with a chlorhexidine-alcohol solution (Level I Evidence, Level 1A Recommendation; TABLE).

Antibiotic prophylaxis

Questions to consider regarding antibiotic prophylaxis for cesarean delivery include appropriateness of treatment, antibiotic(s) selection, timing of administration, dose, and special circumstances.

Should you give the patient prophylactic antibiotics?

Prophylactic antibiotics are justified for surgical procedures whenever 3 major criteria are met⁵:

1. the surgical site is inevitably contaminated with bacteria
2. in the absence of prophylaxis, the frequency of infection at the operative site is unacceptably high
3. operative site infections have the potential to lead to serious, potentially life-threatening sequelae.

Without a doubt, all 3 of these criteria are fulfilled when considering either urgent or nonurgent cesarean delivery. When cesarean delivery follows a long labor complicated by ruptured membranes, multiple internal vaginal examinations, and internal fetal monitoring, the operative site is inevitably contaminated with hundreds of thousands of pathogenic bacteria. Even when cesarean delivery is scheduled to occur before the onset of labor and ruptured membranes, a high concentration of vaginal organisms is introduced into the uterine and pelvic cavities coincident with making the hysterotomy incision.⁶

In the era before prophylactic antibiotics were used routinely, postoperative infection rates in some highly indigent patient populations approached 85%.⁵ Finally, as noted previously, postcesarean endometritis may progress to pelvic abscess formation, septic pelvic vein thrombophlebitis, and septic shock; wound infections may be complicated by dehiscence and evisceration.

When should you administer antibiotics: Before the surgical incision or after cord clamping?

More than 50 years ago, Burke conducted the classic sequence of basic science experiments that forms the foundation for use of prophylactic antibiotics.⁷ Using a guinea pig model, he showed that prophylactic antibiotics exert their most pronounced effect when they are administered before the surgical incision is made and before bacterial contamination occurs. Prophylaxis that is delayed more than 4 hours after the start of surgery will likely be ineffective.

Interestingly, however, when clinicians first began using prophylactic antibiotics for cesarean delivery, some investigators expressed concern about the possible exposure of the neonate to antibiotics just before delivery—specifically, whether this exposure would increase the frequency of evaluations for suspected sepsis or would promote resistance among organisms that would make neonatal sepsis more difficult to treat.

Gordon and colleagues published an important report in 1979 that showed that preoperative administration of ampicillin did not increase the frequency of immediate or delayed neonatal infections.⁸ However, delaying the administration of ampicillin until after the umbilical cord was clamped was just as effective in preventing post‑cesarean endometritis. Subsequently, Cunningham and co-workers showed that preoperative administration of prophylactic antibiotics significantly increased the frequency of sepsis workups in exposed neonates compared with infants with no preoperative antibiotic exposure (28% vs 15%; P<.025).⁹ Based on these 2 reports, obstetricians adopted a policy of delaying antibiotic administration until after the infant’s umbilical cord was clamped.

In 2007, Sullivan and colleagues challenged this long-standing practice.¹⁰ In a carefully designed prospective, randomized, double-blind trial, they showed that patients who received preoperative cefazolin had a significant reduction in the frequency of endometritis compared with women who received the same antibiotic after cord clamping (1% vs 5%; RR, 0.2; 95% CI, 0.2–0.94). The rate of wound infection was lower in the preoperative antibiotic group (3% vs 5%), but this difference did not reach statistical significance. The total infection-related morbidity was significantly reduced in women who received antibiotics preoperatively (4.0% vs 11.5%; RR, 0.4; 95% CI, 0.18–0.87). Additionally, there was no increase in the frequency of proven or suspected neonatal infection in the infants exposed to antibiotics before delivery.

Subsequent to the publication by Sullivan and colleagues, other reports have confirmed that administration of antibiotics prior to surgery is superior to administration after clamping of the umbilical cord.^10–12 Thus, we have come full circle back to Burke’s principle established more than a half century ago.⁷

Which antibiotic(s) should you administer for prophylaxis, and how many doses?

In an earlier review, one of us (PD) examined the evidence regarding choice of antibiotics and number of doses, concluding that a single dose of a first-generation cephalosporin, such as cefazolin, was the preferred regimen.⁵ The single dose was comparable in effectiveness to 2- or 3-dose regimens and to single- or multiple-dose regimens of broader-spectrum agents. For more than 20 years now, the standard of care for antibiotic prophylaxis has been a single 1- to 2-g dose of cefazolin.

Several recent reports, however, have raised the question of whether the prophylactic effect could be enhanced if the spectrum of activity of the antibiotic regimen was broadened to include an agent effective against Ureaplasma species.

Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection; they showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis.¹³ In a follow-up report from the same institution, Tita and co-workers demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.¹⁴ In both of these investigations, the antibiotics were administered after cord clamping.

In a subsequent report, Ward and Duff¹⁵ showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a very low rate of both endometritis and wound infection in a population similar to that studied by Tita et al.^13,14

Very recently, Tita and associates published the results of the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial conducted at 14 US hospitals.¹⁶ This study included 2,013 women undergoing cesarean delivery during labor or after membrane rupture who were randomly assigned to receive intravenous azithromycin 500 mg (n = 1,019) or placebo (n = 994). All women also received standard antibiotic prophylaxis with cefazolin. The primary outcome (a composite of endometritis, wound infection, or other infection within 6 weeks) was significantly lower in the azithromycin group than in the placebo group (6.1% vs 12.0%, P<.001). In addition, there were significant differences between the treatment groups in the rates of endometritis (3.8% in the azithromycin group vs 6.1% in the placebo group, P = .02) as well as in the rates of wound infection (2.4% vs 6.6%, respectively, P<.001). Of additional note, there were no differences between the 2 groups in the composite neonatal outcome of death and serious neonatal complications (14.3% vs 13.6%, P = .63).The investigators concluded that extended-spectrum prophylaxis with adjunctive azithromycin safely reduces infection rates without raising the risk of neonatal adverse outcomes.

What the evidence says

We conclude that all patients, even those having a scheduled cesarean before the onset of labor or ruptured membranes, should receive prophylactic antibiotics in a single dose administered preoperatively rather than after cord clamping (Level I Evidence, Level 1A Recommendation; TABLE). In high-risk populations (eg, women in labor with ruptured membranes who are having an urgent cesarean), for whom the baseline risk of infection is high, administer the combination of cefazolin plus azithromycin in lieu of cefazolin alone (Level I Evidence, Level 1A Recommendation; TABLE).

If the patient has a history of an immediate hypersensitivity reaction to beta-lactam antibiotics, we recommend the combination of clindamycin (900 mg) plus gentamicin (1.5 mg/kg) as a single infusion prior to surgery. We base this recommendation on the need to provide reasonable coverage against a broad range of pathogens. Clindamycin covers gram-positive aerobes, such as staphylococci species and group B streptococci, and anaerobes; gentamicin covers aerobic gram-negative bacilli. A single agent, such as clindamycin or metronidazole, does not provide the broad-based coverage necessary for effective prophylaxis (Level III Evidence, Level 1C Recommendation; TABLE).

If the patient is overweight or obese, should you modify the antibiotic dose?

The prevalence of obesity in the United States continues to increase. One-third of all US reproductive-aged women are obese, and 6% of women are extremely obese.¹⁷ Obesity increases the risk of postcesarean infection 3- to 5- fold.¹⁸ Because both pregnancy and obesity increase the total volume of a drug’s distribution, achieving adequate antibiotic tissue concentrations may be hindered by a dilutional effect. Furthermore, pharmacokinetic studies consistently have shown that the tissue concentration of an antibiotic—which, ideally, should be above the minimum inhibitory concentration (MIC) for common bacteria—determines the susceptibility of those tissues to infection, regardless of whether the serum concentration of the antibiotic is in the therapeutic range.¹⁹

These concerns have led to several recent investigations evaluating different doses of cefazolin for obese patients. Pevzner and colleagues conducted a prospective cohort study of 29 women having a scheduled cesarean delivery.²⁰ The patients were divided into 3 groups: lean (BMI <30 kg m²), obese (BMI 30.0–39.9 kg m²), and extremely obese (BMI >40 kg m²). All women received a 2-g dose of cefazolin 30 to 60 minutes before surgery. Cefazolin concentrations in adipose tissue obtained at the time of skin incision were inversely proportional to maternal BMI (r, −0.67; P<.001). All specimens demonstrated a therapeutic concentration (>1 µg/g) of cefazolin for gram-positive cocci, but 20% of the obese women and 33% of the extremely obese women did not achieve the MIC (>4 µg/g) for gram-negative bacilli (P = .29 and P = .14, respectively). At the time of skin closure, 20% of obese women and 44% of extremely obese women did not have tissue concentrations that exceeded the MIC for gram-negative bacteria.

Swank and associates conducted a prospective cohort study that included 28 women.¹⁸ They demonstrated that, after a 2-g dose of cefazolin, only 20% of the obese women (BMI 30–40 kg m²) and 0% of the extremely obese women (BMI >40 kg m²) achieved an adipose tissue concentration that exceeded the MIC for gram-negative rods (8 µg/mL). However, 100% and 71.4%, respectively, achieved such a tissue concentration after a 3-g dose. When the women were stratified by actual weight, there was a statistically significant difference between those who weighed less than 120 kg and those who weighed more than 120 kg. Seventy-nine percent of the former had a tissue concentration of cefazolin greater than 8 µg/mL compared with 0% of the women who weighed more than 120 kg. Based on these observations, the authors recommended a 3-g dose of cefazolin for women who weigh more than 120 kg.

In a double-blind RCT with 26 obese women (BMI ≥30 kg m²), Young and colleagues demonstrated that, at the time of hysterotomy and fascial closure, significantly higher concentrations of cefazolin were found in the adipose tissue of obese women who received a 3-g dose of antibiotic compared with those who received a 2-g dose.²¹ However, all concentrations of cefazolin were consistently above the MIC of cefazolin for gram-positive cocci (1 µg/g) and gram-negative bacilli (4 µg/g). Further, Maggio and co-workers conducted a double-blind RCT comparing a 2-g dose of cefazolin versus a 3-g dose in 57 obese women (BMI ≥30 kg m²).²² They found no statistically significant difference in the percentage of women who had tissue concentrations of cefazolin greater than the MIC for gram-positive cocci (8 µg/g). All samples were above the MIC of cefazolin for gram-negative bacilli (2 µg/g). Based on these data, these investigators did not recommend increasing the dose of cefazolin from 2 g to 3 g in obese patients.^21,22

The studies discussed above are difficult to compare for 3 reasons. First, each study used a different MIC of cefazolin for both gram-positive and gram-negative bacteria. Second, the authors sampled different maternal tissues or serum at varying times during the cesarean delivery. Third, the studies did not specifically investigate, or were not powered sufficiently to address, the more important clinical outcome of surgical site infection. In a recent historical cohort study, Ward and Duff were unable to show that increasing the dose of cefazolin to 2 g in all women with a BMI <30 kg m² and to 3 g in all women with a BMI >30 kg m² reduced the rate of endometritis and wound infection below the level already achieved with combined prophylaxis with cefazolin (1 g) plus azithromycin (500 mg).¹⁵

Sutton and colleagues recently assessed the pharmacokinetics of azithromycin when used as prophylaxis for cesarean delivery.²³ They studied 30 women who had a scheduled cesarean delivery and who received a 500-mg intravenous dose of azithromycin that was initiated 15, 30, or 60 minutes before the surgical incision and then infused over 1 hour. They obtained maternal plasma samples multiple times during the first 8 hours after surgery. They also obtained samples of amniotic fluid, placenta, myometrium, adipose tissue, and umbilical cord blood intraoperatively. The median concentration of azithromycin in adipose tissue was 102 ng/g, which is below the MIC₅₀ for Ureaplasma species (250 ng/mL). The median concentration in myometrial tissue was 402 ng/g. The concentration in maternal plasma consistently exceeded the MIC₅₀ for Ureaplasma species.

What the evidence says

All women, regardless of weight, who will undergo cesarean delivery should receive a 2-g dose of cefazolin (Level II Evidence, Level 1B Recommendation; TABLE).If azithromycin is used in combination with cefazolin, an intravenous dose of 500 mg appears to provide adequate concentrations in serum and myometrium, but probably not in adipose tissue. More information is needed before we can make a firm recommendation about weight-based dosing of azithromycin.

CASE Resolved

For the 26-year-old obese laboring patient about to undergo cesarean delivery, reasonable steps for prevention of infection include removing the hair at the incision site with clippers or depilatory cream immediately prior to the start of surgery; cleansing the abdomen with a chlorhexidine-alcohol solution; and administering cefazolin (2 g) plus azithromycin (500 mg) preoperatively.

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

EXPERT COMMENTARY

John M. Thorp Jr, MD, McAllister Distinguished Professor, Division Director, General Obstetrics and Gynecology, Vice Chair of Research, Department of Ob-Gyn, University of North Carolina Schools of Medicine and Public Health, Chapel Hill.

Five years ago one of our interns operating with the director of labor and delivery challenged him as to why we were not using evidenced-based surgical techniques for cesarean delivery. Bruised by the formidable (and at times misleading) club of “evidence-based medicine” that is held as sacrosanct by the modern obstetrician, the director responded to the charge by researching a systematic review on abdominal delivery that amalgamated studies of poor quality with precious few trials. He unilaterally decided that we needed an opening in the transparent portion of the drape overlying the incision site so that we might use “evidence” to prevent operative site infection. The end result: No change in the incidence of wound infections, and adhesive drapes that did not adhere well, thereby displacing the effluent of amniotic fluid and blood that are part of a cesarean delivery back into the first assistant’s socks, shoes, and clothing. It was as if the clock had been turned back to my early years as an attending when we had cloth drapes. So much for having an evidence-based protocol. I was thus elated at reading the results of the CORONIS trial.

Details of the study

The CORONIS trial, in which investigators randomly assigned almost 16,000 women from 7 countries (Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan), used a sophisticated factorial design and followed up 13,153 (84%) of the women for 3 years. The investigators tested an array of technical questions about 5 intervention pairs used during abdominal delivery and reported the main outcomes of interest for each intervention, including:

• blunt versus sharp abdominal entry—no evidence of a difference in risk of abdominal hernias (adjusted risk ratio [RR], 0.66; 95% confidence interval [CI], 0.39–1.11)
• exteriorization of the uterus versus intra-abdominal repair—no evidence of a difference in risk of infertility (RR, 0.91; 95% CI, 0.71–1.18) or of ectopic pregnancy (RR, 0.50; CI, 0.15–1.66)
• single- versus double-layer closure of the uterus—no evidence of a difference in maternal death (RR, 0.78; 95% CI, 0.46–1.32) or a composite of pregnancy complications (RR, 1.20; 95% CI, 0.75–1.90)
• closure versus nonclosure of the peritoneum—no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions, such as infertility (RR, 0.8; 95% CI, 0.61–1.06)
• chromic catgut versus polyglactin-910 sutures—no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (RR, 3.05; 95% CI, 0.32–29.29).

Strengths and limitations. The CORONIS trial included a large number of participants and had comprehensive follow-up, a rigorous data collection process, and the participation of many countries. The trial’s participating centers, however, were mostly large referral hospitals with high research interest; adverse outcomes might have been higher in other settings. As well, a lower incidence of subsequent pregnancy among participants limited the study’s power to detect differences in outcomes between the intervention pairs.

Conclusions. None of the alternative techniques produced any real benefits despite syntheses-suggested benefit reported in systematic reviews. Surgeon preference for cesarean delivery techniques likely will continue to guide clinical practice along with economic and institution factors.

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

EXPERT COMMENTARY

John M. Thorp Jr, MD, McAllister Distinguished Professor, Division Director, General Obstetrics and Gynecology, Vice Chair of Research, Department of Ob-Gyn, University of North Carolina Schools of Medicine and Public Health, Chapel Hill.

Five years ago one of our interns operating with the director of labor and delivery challenged him as to why we were not using evidenced-based surgical techniques for cesarean delivery. Bruised by the formidable (and at times misleading) club of “evidence-based medicine” that is held as sacrosanct by the modern obstetrician, the director responded to the charge by researching a systematic review on abdominal delivery that amalgamated studies of poor quality with precious few trials. He unilaterally decided that we needed an opening in the transparent portion of the drape overlying the incision site so that we might use “evidence” to prevent operative site infection. The end result: No change in the incidence of wound infections, and adhesive drapes that did not adhere well, thereby displacing the effluent of amniotic fluid and blood that are part of a cesarean delivery back into the first assistant’s socks, shoes, and clothing. It was as if the clock had been turned back to my early years as an attending when we had cloth drapes. So much for having an evidence-based protocol. I was thus elated at reading the results of the CORONIS trial.

Details of the study

The CORONIS trial, in which investigators randomly assigned almost 16,000 women from 7 countries (Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan), used a sophisticated factorial design and followed up 13,153 (84%) of the women for 3 years. The investigators tested an array of technical questions about 5 intervention pairs used during abdominal delivery and reported the main outcomes of interest for each intervention, including:

• blunt versus sharp abdominal entry—no evidence of a difference in risk of abdominal hernias (adjusted risk ratio [RR], 0.66; 95% confidence interval [CI], 0.39–1.11)
• exteriorization of the uterus versus intra-abdominal repair—no evidence of a difference in risk of infertility (RR, 0.91; 95% CI, 0.71–1.18) or of ectopic pregnancy (RR, 0.50; CI, 0.15–1.66)
• single- versus double-layer closure of the uterus—no evidence of a difference in maternal death (RR, 0.78; 95% CI, 0.46–1.32) or a composite of pregnancy complications (RR, 1.20; 95% CI, 0.75–1.90)
• closure versus nonclosure of the peritoneum—no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions, such as infertility (RR, 0.8; 95% CI, 0.61–1.06)
• chromic catgut versus polyglactin-910 sutures—no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (RR, 3.05; 95% CI, 0.32–29.29).

Strengths and limitations. The CORONIS trial included a large number of participants and had comprehensive follow-up, a rigorous data collection process, and the participation of many countries. The trial’s participating centers, however, were mostly large referral hospitals with high research interest; adverse outcomes might have been higher in other settings. As well, a lower incidence of subsequent pregnancy among participants limited the study’s power to detect differences in outcomes between the intervention pairs.

Conclusions. None of the alternative techniques produced any real benefits despite syntheses-suggested benefit reported in systematic reviews. Surgeon preference for cesarean delivery techniques likely will continue to guide clinical practice along with economic and institution factors.

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

EXPERT COMMENTARY

John M. Thorp Jr, MD, McAllister Distinguished Professor, Division Director, General Obstetrics and Gynecology, Vice Chair of Research, Department of Ob-Gyn, University of North Carolina Schools of Medicine and Public Health, Chapel Hill.

Five years ago one of our interns operating with the director of labor and delivery challenged him as to why we were not using evidenced-based surgical techniques for cesarean delivery. Bruised by the formidable (and at times misleading) club of “evidence-based medicine” that is held as sacrosanct by the modern obstetrician, the director responded to the charge by researching a systematic review on abdominal delivery that amalgamated studies of poor quality with precious few trials. He unilaterally decided that we needed an opening in the transparent portion of the drape overlying the incision site so that we might use “evidence” to prevent operative site infection. The end result: No change in the incidence of wound infections, and adhesive drapes that did not adhere well, thereby displacing the effluent of amniotic fluid and blood that are part of a cesarean delivery back into the first assistant’s socks, shoes, and clothing. It was as if the clock had been turned back to my early years as an attending when we had cloth drapes. So much for having an evidence-based protocol. I was thus elated at reading the results of the CORONIS trial.

Details of the study

The CORONIS trial, in which investigators randomly assigned almost 16,000 women from 7 countries (Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan), used a sophisticated factorial design and followed up 13,153 (84%) of the women for 3 years. The investigators tested an array of technical questions about 5 intervention pairs used during abdominal delivery and reported the main outcomes of interest for each intervention, including:

• blunt versus sharp abdominal entry—no evidence of a difference in risk of abdominal hernias (adjusted risk ratio [RR], 0.66; 95% confidence interval [CI], 0.39–1.11)
• exteriorization of the uterus versus intra-abdominal repair—no evidence of a difference in risk of infertility (RR, 0.91; 95% CI, 0.71–1.18) or of ectopic pregnancy (RR, 0.50; CI, 0.15–1.66)
• single- versus double-layer closure of the uterus—no evidence of a difference in maternal death (RR, 0.78; 95% CI, 0.46–1.32) or a composite of pregnancy complications (RR, 1.20; 95% CI, 0.75–1.90)
• closure versus nonclosure of the peritoneum—no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions, such as infertility (RR, 0.8; 95% CI, 0.61–1.06)
• chromic catgut versus polyglactin-910 sutures—no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (RR, 3.05; 95% CI, 0.32–29.29).

Strengths and limitations. The CORONIS trial included a large number of participants and had comprehensive follow-up, a rigorous data collection process, and the participation of many countries. The trial’s participating centers, however, were mostly large referral hospitals with high research interest; adverse outcomes might have been higher in other settings. As well, a lower incidence of subsequent pregnancy among participants limited the study’s power to detect differences in outcomes between the intervention pairs.

Conclusions. None of the alternative techniques produced any real benefits despite syntheses-suggested benefit reported in systematic reviews. Surgeon preference for cesarean delivery techniques likely will continue to guide clinical practice along with economic and institution factors.

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

In a web-focused world, it should not take much convincing that monitoring your online reputation is time well spent. For some of us, it may be hard to believe that online reviews have evolved beyond restaurants and plumbers, but today your patients are flocking to the Internet to read and leave reviews about you, your staff, and your services. What can you do to protect your online reputation?

We first addressed this topic in December 2014 (“Using the Internet in your practice. Part 4: Reputation management—how to gather kudos and combat negative online reviews”¹). Have you implemented any of the tactics we offered then? We hope that you do take proactive steps to protect your online image.

What is a physician’s most precious asset?

You might answer this question with, “my patients” or “the training and education that I have obtained to practice my craft.” But the real answer is that your most precious asset is your reputation.

Physicians live and die by their reputations. We spend our entire medical careers polishing and protecting this status. The Internet dramatically has altered the way people gather information. It is sad but true that a single comment that only takes a few seconds and a single mouse-click to post can be seen by thousands and ruin that life-long effort.

How are physicians rated on the web?

Online physician reviews are positive 70% to 90% of the time.² Most physicians have 5 or fewer reviews on any one site.³ Of the approximately 30 sites that monitor physicians and hospitals online, one of the most popular is AngiesList.com. This site requires registration and a fee; a member can review a physician every 6 months. On free websites such as Yelp.com and doctorsscorecard.com the reviewer can comment once. Other sites such as vitals.com or DrScore.com limit the reviews from 1 source, which prevents an angry patient from stuffing the ballot box.²

Pay attention

At a minimum, physicians should be monitoring their reputation by conducting periodic searches—“Googling” their name and practice name—to identify what information is already online. You may find that 3, 4, or even 10 reviews appear on various sites. If you are lucky, these reviews will be positive. Don’t be surprised, however, if 1 or 2 are not. Let’s face it: even the most accredited and experienced physician cannot possibly satisfy every patient who walks through the door.

Tell your own story

As physicians, you may not have control over what others say about you, but you can take ownership of your online presence by establishing a website, blog, and social media platforms, ensuring your story is being properly communicated. Without an online presence, you are entirely at the mercy of directory and review sites.

Optimize your website

A site that successfully uses search engine optimization (SEO) will have the upper hand when patients hunt for a physician in your area because the information will be posted at the top of the search page, well above the reviews and listings left by patients and other third-party sources. This is a critical step for your online brand because it will be difficult for other sites to mask your credibility. This should motivate you to develop an online presence, regularly update information, and participate in Internet dialog with other sites.

Generate quality, natural reviews

If your site is in good standing in search results, the next step is to implement a patient reviews strategy to start acquiring positive online reviews. A third-party provider can work with you to launch a local search engine optimization strategy and a natural reviews management program tailored for your practice’s needs. For the most part, however, we do not recommend using an online reputation management company. It is far better and more economical to ask satisfied patients to provide reviews.

At first, you may be tempted to actively petition or solicit reviews through survey software, but this method is manipulative and can lead to reputation problems for your practice. Google actively tracks where reviews originate and uses advanced algorithms to determine the review’s integrity. A petitioned review is classified as less valid, and therefore Google will assume it was not written under the same pretense as a natural, unsolicited review.

Quality customer service and outstanding patient care are often what achieve the organic reviews you are striving for. To encourage a steady flow, administer a process that encourages your most satisfied, loyal patients to review your practice.

Keep the process simple. Capture positive compliments at the point of service. Before a patient leaves your office, hand her a card (FIGURE) with easy steps for posting an online review, or offer her a tablet that links directly to your website review section. If your patient is not computer savvy, ask her to complete a 4- to 5-question survey and give her a clipboard and a pen. Then have a staff member post it on your website.

In Dr. Baum’s practice, there is a poster in every exam room and in the reception area where patients can scan the quick response (QR) code and immediately submit a testimonial. Using this system, the practice is able to collect 3 to 5 positive reviews every day.

A patient pleased with your staff’s service will happily take 5 minutes to submit a review. Acquire 5 to 10 reviews monthly and within a year’s time you will have generated enough positive reviews to negate any damaging comments that inevitably will emerge from time to time.

The bottom line

Patients are seeking and leaving reviews about you and your practice online and you need to actively manage your online reputation. Do not let one disgruntled patient ruin your reputation. Our advice: Do not wait for a negative review to begin your reputation management. Take an active role and generate positive reviews to drown out negative remarks made by an occasional patient. This is an inexpensive process that does work.

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

In a web-focused world, it should not take much convincing that monitoring your online reputation is time well spent. For some of us, it may be hard to believe that online reviews have evolved beyond restaurants and plumbers, but today your patients are flocking to the Internet to read and leave reviews about you, your staff, and your services. What can you do to protect your online reputation?

We first addressed this topic in December 2014 (“Using the Internet in your practice. Part 4: Reputation management—how to gather kudos and combat negative online reviews”¹). Have you implemented any of the tactics we offered then? We hope that you do take proactive steps to protect your online image.

What is a physician’s most precious asset?

You might answer this question with, “my patients” or “the training and education that I have obtained to practice my craft.” But the real answer is that your most precious asset is your reputation.

Physicians live and die by their reputations. We spend our entire medical careers polishing and protecting this status. The Internet dramatically has altered the way people gather information. It is sad but true that a single comment that only takes a few seconds and a single mouse-click to post can be seen by thousands and ruin that life-long effort.

How are physicians rated on the web?

Online physician reviews are positive 70% to 90% of the time.² Most physicians have 5 or fewer reviews on any one site.³ Of the approximately 30 sites that monitor physicians and hospitals online, one of the most popular is AngiesList.com. This site requires registration and a fee; a member can review a physician every 6 months. On free websites such as Yelp.com and doctorsscorecard.com the reviewer can comment once. Other sites such as vitals.com or DrScore.com limit the reviews from 1 source, which prevents an angry patient from stuffing the ballot box.²

Pay attention

At a minimum, physicians should be monitoring their reputation by conducting periodic searches—“Googling” their name and practice name—to identify what information is already online. You may find that 3, 4, or even 10 reviews appear on various sites. If you are lucky, these reviews will be positive. Don’t be surprised, however, if 1 or 2 are not. Let’s face it: even the most accredited and experienced physician cannot possibly satisfy every patient who walks through the door.

Tell your own story

As physicians, you may not have control over what others say about you, but you can take ownership of your online presence by establishing a website, blog, and social media platforms, ensuring your story is being properly communicated. Without an online presence, you are entirely at the mercy of directory and review sites.

Optimize your website

A site that successfully uses search engine optimization (SEO) will have the upper hand when patients hunt for a physician in your area because the information will be posted at the top of the search page, well above the reviews and listings left by patients and other third-party sources. This is a critical step for your online brand because it will be difficult for other sites to mask your credibility. This should motivate you to develop an online presence, regularly update information, and participate in Internet dialog with other sites.

Generate quality, natural reviews

If your site is in good standing in search results, the next step is to implement a patient reviews strategy to start acquiring positive online reviews. A third-party provider can work with you to launch a local search engine optimization strategy and a natural reviews management program tailored for your practice’s needs. For the most part, however, we do not recommend using an online reputation management company. It is far better and more economical to ask satisfied patients to provide reviews.

At first, you may be tempted to actively petition or solicit reviews through survey software, but this method is manipulative and can lead to reputation problems for your practice. Google actively tracks where reviews originate and uses advanced algorithms to determine the review’s integrity. A petitioned review is classified as less valid, and therefore Google will assume it was not written under the same pretense as a natural, unsolicited review.

Quality customer service and outstanding patient care are often what achieve the organic reviews you are striving for. To encourage a steady flow, administer a process that encourages your most satisfied, loyal patients to review your practice.

Keep the process simple. Capture positive compliments at the point of service. Before a patient leaves your office, hand her a card (FIGURE) with easy steps for posting an online review, or offer her a tablet that links directly to your website review section. If your patient is not computer savvy, ask her to complete a 4- to 5-question survey and give her a clipboard and a pen. Then have a staff member post it on your website.

In Dr. Baum’s practice, there is a poster in every exam room and in the reception area where patients can scan the quick response (QR) code and immediately submit a testimonial. Using this system, the practice is able to collect 3 to 5 positive reviews every day.

A patient pleased with your staff’s service will happily take 5 minutes to submit a review. Acquire 5 to 10 reviews monthly and within a year’s time you will have generated enough positive reviews to negate any damaging comments that inevitably will emerge from time to time.

The bottom line

Patients are seeking and leaving reviews about you and your practice online and you need to actively manage your online reputation. Do not let one disgruntled patient ruin your reputation. Our advice: Do not wait for a negative review to begin your reputation management. Take an active role and generate positive reviews to drown out negative remarks made by an occasional patient. This is an inexpensive process that does work.

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

In a web-focused world, it should not take much convincing that monitoring your online reputation is time well spent. For some of us, it may be hard to believe that online reviews have evolved beyond restaurants and plumbers, but today your patients are flocking to the Internet to read and leave reviews about you, your staff, and your services. What can you do to protect your online reputation?

We first addressed this topic in December 2014 (“Using the Internet in your practice. Part 4: Reputation management—how to gather kudos and combat negative online reviews”¹). Have you implemented any of the tactics we offered then? We hope that you do take proactive steps to protect your online image.

What is a physician’s most precious asset?

You might answer this question with, “my patients” or “the training and education that I have obtained to practice my craft.” But the real answer is that your most precious asset is your reputation.

Physicians live and die by their reputations. We spend our entire medical careers polishing and protecting this status. The Internet dramatically has altered the way people gather information. It is sad but true that a single comment that only takes a few seconds and a single mouse-click to post can be seen by thousands and ruin that life-long effort.

How are physicians rated on the web?

Online physician reviews are positive 70% to 90% of the time.² Most physicians have 5 or fewer reviews on any one site.³ Of the approximately 30 sites that monitor physicians and hospitals online, one of the most popular is AngiesList.com. This site requires registration and a fee; a member can review a physician every 6 months. On free websites such as Yelp.com and doctorsscorecard.com the reviewer can comment once. Other sites such as vitals.com or DrScore.com limit the reviews from 1 source, which prevents an angry patient from stuffing the ballot box.²

Pay attention

At a minimum, physicians should be monitoring their reputation by conducting periodic searches—“Googling” their name and practice name—to identify what information is already online. You may find that 3, 4, or even 10 reviews appear on various sites. If you are lucky, these reviews will be positive. Don’t be surprised, however, if 1 or 2 are not. Let’s face it: even the most accredited and experienced physician cannot possibly satisfy every patient who walks through the door.

Tell your own story

As physicians, you may not have control over what others say about you, but you can take ownership of your online presence by establishing a website, blog, and social media platforms, ensuring your story is being properly communicated. Without an online presence, you are entirely at the mercy of directory and review sites.

Optimize your website

A site that successfully uses search engine optimization (SEO) will have the upper hand when patients hunt for a physician in your area because the information will be posted at the top of the search page, well above the reviews and listings left by patients and other third-party sources. This is a critical step for your online brand because it will be difficult for other sites to mask your credibility. This should motivate you to develop an online presence, regularly update information, and participate in Internet dialog with other sites.

Generate quality, natural reviews

If your site is in good standing in search results, the next step is to implement a patient reviews strategy to start acquiring positive online reviews. A third-party provider can work with you to launch a local search engine optimization strategy and a natural reviews management program tailored for your practice’s needs. For the most part, however, we do not recommend using an online reputation management company. It is far better and more economical to ask satisfied patients to provide reviews.

At first, you may be tempted to actively petition or solicit reviews through survey software, but this method is manipulative and can lead to reputation problems for your practice. Google actively tracks where reviews originate and uses advanced algorithms to determine the review’s integrity. A petitioned review is classified as less valid, and therefore Google will assume it was not written under the same pretense as a natural, unsolicited review.

Quality customer service and outstanding patient care are often what achieve the organic reviews you are striving for. To encourage a steady flow, administer a process that encourages your most satisfied, loyal patients to review your practice.

Keep the process simple. Capture positive compliments at the point of service. Before a patient leaves your office, hand her a card (FIGURE) with easy steps for posting an online review, or offer her a tablet that links directly to your website review section. If your patient is not computer savvy, ask her to complete a 4- to 5-question survey and give her a clipboard and a pen. Then have a staff member post it on your website.

In Dr. Baum’s practice, there is a poster in every exam room and in the reception area where patients can scan the quick response (QR) code and immediately submit a testimonial. Using this system, the practice is able to collect 3 to 5 positive reviews every day.

A patient pleased with your staff’s service will happily take 5 minutes to submit a review. Acquire 5 to 10 reviews monthly and within a year’s time you will have generated enough positive reviews to negate any damaging comments that inevitably will emerge from time to time.

The bottom line

Patients are seeking and leaving reviews about you and your practice online and you need to actively manage your online reputation. Do not let one disgruntled patient ruin your reputation. Our advice: Do not wait for a negative review to begin your reputation management. Take an active role and generate positive reviews to drown out negative remarks made by an occasional patient. This is an inexpensive process that does work.

Share your thoughts! 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 download the PDF.

Key learning objectives

The faculty for this roundtable aim to:

1. Explain the process for bringing an innovation to market, including the roles of surgeon inventor, engineer, manufacturer, and industry
2. Discuss best practices, based on lessons learned, when pursuing an innovative idea for patient care
3. Articulate ways to improve upon the entire development process for new techniques, devices, etc, being brought to the FDA for possible approval and to market for patient use.

Click here to download the PDF.

Key learning objectives

The faculty for this roundtable aim to:

1. Explain the process for bringing an innovation to market, including the roles of surgeon inventor, engineer, manufacturer, and industry
2. Discuss best practices, based on lessons learned, when pursuing an innovative idea for patient care
3. Articulate ways to improve upon the entire development process for new techniques, devices, etc, being brought to the FDA for possible approval and to market for patient use.

Click here to download the PDF.

Key learning objectives

The faculty for this roundtable aim to:

1. Explain the process for bringing an innovation to market, including the roles of surgeon inventor, engineer, manufacturer, and industry
2. Discuss best practices, based on lessons learned, when pursuing an innovative idea for patient care
3. Articulate ways to improve upon the entire development process for new techniques, devices, etc, being brought to the FDA for possible approval and to market for patient use.

NEW LNG IUS: GOOD FOR 5 YEARS

FOR MORE INFORMATION, VISIT:
https://hcp.kyleena-us.com/

EASIER LAPAROSCOPIC ACCESS

To use LapCap₂, says Life Care, center it over the umbilicus, attach a hose to the suction port, and apply negative pressure. The abdomen immediately rises for Veress needle insertion. Inert gas is then delivered to replace the negative pressure, and the procedure can continue.

FOR MORE INFORMATION, VISIT:
http://www.lcmd.com/products/lapcap2

NEW LNG IUS: GOOD FOR 5 YEARS

FOR MORE INFORMATION, VISIT:
https://hcp.kyleena-us.com/

EASIER LAPAROSCOPIC ACCESS

To use LapCap₂, says Life Care, center it over the umbilicus, attach a hose to the suction port, and apply negative pressure. The abdomen immediately rises for Veress needle insertion. Inert gas is then delivered to replace the negative pressure, and the procedure can continue.

FOR MORE INFORMATION, VISIT:
http://www.lcmd.com/products/lapcap2

NEW LNG IUS: GOOD FOR 5 YEARS

FOR MORE INFORMATION, VISIT:
https://hcp.kyleena-us.com/

EASIER LAPAROSCOPIC ACCESS

To use LapCap₂, says Life Care, center it over the umbilicus, attach a hose to the suction port, and apply negative pressure. The abdomen immediately rises for Veress needle insertion. Inert gas is then delivered to replace the negative pressure, and the procedure can continue.

FOR MORE INFORMATION, VISIT:
http://www.lcmd.com/products/lapcap2

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

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

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

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

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

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

Access Dr. Burkman's Webcasts on contraception:

• Hormonal contraception and risk of venous thromboembolism
• Oral contraceptives and breast cancer: What’s the risk?
• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resources for your practice:

• Book recommendation: Allen RH, Cwiak CA, eds. Contraception for the medically challenging patient. New York, New York: Springer New York; 2014.
• United States Medical Eligibility Criteria for Contraceptive Use, 2016
• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use, 2010
• Summary Chart of US Medical Eligibility for Contraceptive Use

Access Dr. Burkman's Webcasts on contraception:

• Hormonal contraception and risk of venous thromboembolism
• Oral contraceptives and breast cancer: What’s the risk?
• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resources for your practice:

• Book recommendation: Allen RH, Cwiak CA, eds. Contraception for the medically challenging patient. New York, New York: Springer New York; 2014.
• United States Medical Eligibility Criteria for Contraceptive Use, 2016
• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use, 2010
• Summary Chart of US Medical Eligibility for Contraceptive Use

Access Dr. Burkman's Webcasts on contraception:

• Hormonal contraception and risk of venous thromboembolism
• Oral contraceptives and breast cancer: What’s the risk?
• Factors that contribute to overall contraceptive efficacy and risks
• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resources for your practice:

• Book recommendation: Allen RH, Cwiak CA, eds. Contraception for the medically challenging patient. New York, New York: Springer New York; 2014.
• United States Medical Eligibility Criteria for Contraceptive Use, 2016
• United States Medical Eligibility Criteria (US MEC) for Contraceptive Use, 2010
• Summary Chart of US Medical Eligibility for Contraceptive Use