Perspectives on Adhesions Following Cesarean Delivery (Slides With Transcript)

Michael Diamond, MD: Hello, I'm Dr. Michael Diamond, Professor and Associate Chair in the Department of Obstetrics and Gynecology at Wayne State University in Detroit, Michigan. I'd like to welcome you to this Medscape CME/CE spotlight panel discussion on "Perspectives on Adhesions Following Cesarean [Delivery]."

Before we begin, I'm joined today for this discussion panel by my colleagues, Dr. Julia Johnson, Professor and Chair of the Department of Obstetrics and Gynecology at the University of Massachusetts; Dr. Wright Bates, Associate Professor from the Division of Reproductive Endocrinology at the University of Alabama at Birmingham; and Dr. Deirdre Lyell, Assistant Professor of Maternal-Fetal Medicine from Stanford University, Palo Alto, California.

Adhesion disease is one of the most frequent complications of abdominal pelvic surgery. The conditions that occur, the adhesions that develop, can have implications for a patient's lifetime; they can significantly impact their quality of life. This can include physical, psychological, economic consequences, which continue to be documented. In particular, recent questions have come up as to whether adhesive disease associated with cesarean sections can have adverse effects on both the patient and on the delivery of the fetus. Greater emphasis should be placed on the study of prevention of adhesive disease and educating patients and healthcare providers about the risk associated with repeat cesarean sections.

The learning objectives for this session will include topics of the potential effects of postoperative adhesion development associated with cesarean sections and their effects on the patient and delivery of the fetus. We'll also identify some of the patients particularly at risk for postoperative adhesion development. We'll review the limited existing data that does exist related to adhesion occurrence after cesarean sections. We'll discuss therapeutic approaches for reducing postoperative adhesion development associated with gynecologic surgeries and explore the applicability of extrapolating existing data about therapeutic agents after cesarean sections.

The first question I would like to address is why do we care about adhesions. Dr. Johnson, why should we care?

Julia Johnson, MD: We care because the incidence of C-sections has increased markedly. We all know that there are an increased number of C-sections. If you compare to 1966, only 4.5% of deliveries were C-section, whereas in 2006, 31% of deliveries were by C section. There's also as we know an increase in repeat C-sections. Eighty-nine percent of women who've had 1 C section -- in a study done in 2003 -- elected to have a repeat C section, meaning that only 11% of women attempted to have vaginal delivery.

The downside of any kind of surgical procedure is that it increases the risk of adhesion formation, with problems related to chronic pelvic pain, possible small bowel obstructions, and increased complexity for subsequent surgeries. And so for that reason we really have to consider what cesarean sections are doing to the women that we serve. The other issue for infertility specialties, of course, is what effect the cesarean section may have on future fertility.

Michael Diamond, MD: Dr. Lyle, perhaps you can share with us your thoughts about why adhesions develop. How do they form?

Deirdre Lyell, MD: We know that tissue ischemia is a predisposing factor to any adhesion. This can result in the suppression of fibrinolysis, and then that results in the persistence of fibrin. Also there's some pretty good data that hypoxia itself -- this is from your work -- can convert fibroblasts into a different phenotype: myofibroblasts, the phenotype that is found within adhesions. We know also other factors probably play a role, such as immunosuppression, deficient immunity, a relative suppression, or just an overwhelmed immune system.

Michael Diamond, MD: Dr. Bates, other thoughts about etiology of adhesion development?

Wright Bates, MD: On the clinical front, extrapolating this damage to a normal system, we need the healing process. But when aberrant pathways occur due to tissue damage, adhesions form. On the clinical side we see this with rough handling of the tissue with excessive use of electrocautery. We're all concerned about leaving foreign products, classically glove powder, and using lap sponges that are rough and dry. There are even anecdotal reports of odd sources of peritoneal injury, such as an overaggressive umbilical piercing leading to small bowel obstruction from adhesion formation. Even drying of the peritoneum at laparoscopy, or the pneumoperitoneum that we all use so we can visualize structures, may damage the normal healing process and lead to adhesions.

Michael Diamond, MD: In my mind the time period that is critical for adhesion development is probably the first 3-5 days after a surgical procedure, which is the time that it was required in most situations for remesothelialization. It is that initial couple of days which is going to be crucial to whether or not adhesions develop.

Wright Bates, MD: Blood is a routine part of surgery and we all attempt to have meticulous hemostasis. Clearly, residual blood, especially in the presence of infection, exacerbates the problem.

Michael Diamond, MD: And tissue injury, as well.

Michael Diamond, MD: Dr. Lyell, any thoughts about changes unique to pregnancy which may either predispose or tend to reduce the likelihood of adhesion development after cesarean sections?

Deirdre Lyell, MD: There are a few. Actually this gets to sort of the question of why the pattern of adhesions that we see at cesarean may be different than what we see in gynecologic surgeries. First, we know that there's fibrinolytic activity in the amitotic fluid -- it's been reported after about 37 weeks -- and so that may play a role once the baby is delivered and the surgical site is repaired in what happens in terms of the development of adhesions. There is increased plasminogen activator activity during pregnancy as well, and we know that that is generally associated with fewer adhesions. Whether this plays a role postdelivery is not clear, but it may play a protective role. We know that the hormonal changes in pregnancy may also play a role, and it's not been entirely elucidated. The effect of estrogen, for example, in laboratory models has been suggestive of an increase in adhesions, but when this was studied clinically that really wasn't found to be thecase. Finally one more is the anatomic effect of the uterus. You've got a very large uterus, and as you mentioned the peritoneum closes generally between about 3-5 days postdelivery, and having that large uterus within that peritoneal defect may play a role in terms of disrupting the mesothelial matrix and leading to some fibrinization.

Michael Diamond, MD: Another thought that I've always had about pregnancy is what happens with the tubes and ectopic pregnancies. It's been my anecdotal experience that I'm less likely to get adhesions to the tube after treatment of an ectopic pregnancy with linear salpingostomy, than I do after fimbrioplasties or other types of tubal surgery, adding further credence to what you've just been describing, of a potential role of pregnancy itself modulating the adhesion development process.

Wright Bates, MD: I also worry at the time of C-section because of the residual blood and fluid. It's clearly not a dry procedure. And if you think about foreign bodies, we use a lot of suture to achieve hemostasis and often we deal with infection or chorioamnionitis. There are factors that predispose to adhesion formation, as well as those that might prevent.

Julia Johnson, MD: Clearly the whole goal is to deliver the baby as quickly as possible, so attention to gentle tissue handling and other things that will lower the risk of adhesions are not thought of at the time of C-section, as they might be during gynecologic surgery.

Wright Bates, MD: As fertility specialists, we worry that any procedure might impact subsequent fecundity or the ability to get pregnant. Clearly there are psychological concerns, and some of that may be pain. The fear of future fertility is an issue as women delay childbearing. And economics: Fertility care can be expensive, especially if you go to the more aggressive approaches, to assisted reproductive technology. Unfortunately we don't have a great handle on what is the true impact of mode of delivery on subsequent pregnancy. Women decide for a variety of reasons not to have more children. There's not a direct correlation, although there's anecdotal evidence to suggest a C-section may predispose you to -- not infertility -- but subfertility or a decreased fertility.

Michael Diamond, MD: How often do adhesions develop after a cesarean section? Dr. Lyell, what did your study show?

Deirdre Lyell, MD: Our study showed that about two thirds of women had adhesions after cesarean. We looked at women who were undergoing a first repeat cesarean delivery, and overall it was about two thirds. When we looked at subgroups, particularly women for whom the peritoneum was left open, 73% of the patients had adhesions, so it was actually pretty significant. In our study we were looking at women having their first repeat cesarean; we know from other studies, in particular your study, Dr. Bates, that the number of cesareans directly correlates with the incidence of adhesions. I wonder if you can tell us a little bit more about that.

Wright Bates, MD: We excluded patients who had risk factors for adhesions -- those with prior gynecologic surgery, those with known pelvic infections -- and then looked at those undergoing multiple C-sections. And we found after 1 C-section, about half the time, or 46% of the time, patients had adhesions. After 2 C-sections, it was about 3 out of 4. There weren't many patients, but those who had 3 prior C-sections, more than 8 out of 10 had adhesions. An interesting thing, we correlated that with the time to deliver the baby, and we found that it took an additional 5 minutes to deliver the infant after 1 C-section; another 8.5 minutes after 2 C-sections; and in those women who had had 3 prior C-sections, it was almost an additional 20 minutes to deliver the infant because of the C-sections and maybe adhesions.

Michael Diamond, MD: Any thoughts about whether those times related to adhesions as opposed to fibrosis, either in the abdominal wall or in the uterus itself?

Wright Bates, MD: This is a very good question. We wondered if the time to deliver the baby was just a result of distortion of tissue planes and scarring in the abdominal wall. We were able to correlate the time to deliver the baby with the presence or absence of adhesions. Regardless of the number of prior C-sections, the time to deliver a baby directly correlated with the presence of intra-abdominal adhesions. As a fertility doctor we worry about the fallopian tubes, and the fimbria are almost sacred. We only found about 7% of the patients had adhesions that only involved the fallopian tubes. On the other hand, 3 out of 4 involved the anterior abdominal wall, the bowel, the uterus, and omentum, and those are the ones that might delay entering the uterine cavity and might be a hindrance to delivery of the baby.

Julia Johnson, MD: You have to be concerned that if it takes that much longer to proceed with a cesarean delivery that there is potential risk for the infant. You always have to think about that delayed time related to adhesion formation.

Wright Bates, MD: In my earlier life as a small town obstetrician, before my subspecialty training, it seemed to be at 3 in the morning, the lady that has dense adhesions, with little or no backup, and often a tracing that you're worried about. We've all been in those positions, and they are not comfortable.

Michael Diamond, MD: Did either of your studies have sufficient numbers and information to allow looking at whether there was a difference as a function of whether it was a transverse uterine incision, or a low vertical incision, or a classical cesarean section incision -- and incidence of adhesions? Or is that where we still need more data?

Deirdre Lyell, MD: We didn't look at that in my study. I do think we need more data in general. Most cesareans today are going to be low transverse, at least in most areas.

Wright Bates, MD: Likewise the vast majority of our incisions were lower uterine segment, transverse. Now we did go one step further. The question is, it takes longer to deliver the baby that is related to adhesions, but does that have any impact on the fetal well-being?

We were able to look at a few markers. The first we took a pH level of 7.2 and said does it matter whether you had previous C-sections, are the babies more likely to have a low pH? And we found an odds ratio, which is about 2.3. You were more than 2 times more likely to have a lower pH if it was a repeat C-section vs a primary C-section. We then looked further to try to correlate that with Apgar scores, and we did linear correlation and we found that there was a direct linear correlation between the 1 minute Apgar and the umbilical cord pH, and the time to deliver the baby. However, I do have to say that clinically it is hard to know the validity of that. Clearly a pH difference of 0.3 or 0.4 in a large data set like our own reaches statistical significance but is a slight meaningful difference clinically? We did not have any information on the long-term well-being, but we at least suggested there might be a detriment to the baby's well-being.

Michael Diamond, MD: Dr. Lyell, as a maternal fetal medicine specialist, any other thoughts on that topic?

Deirdre Lyell, MD: I do think that is a very important finding, that there was a different in the pH. I think we've all been in situations where there's a need to get the baby out urgently, if not emergently. With a C-section rate at 31%, and most women opting for repeat cesarean, it's really only a matter of time when we run into a situation where we urgently need to get a baby out and are unable to do so, perhaps because of adhesions. As an obstetrician, I can tell you when the heart rate tracing is down and things like that, you will just go as quickly as possible. It's really a matter of time, I think, until we start to see women who have an increased rate of bowel injury because of this, or we will see babies that are compromised as a result of just delay of delivery. If it takes 18 minutes at someone's fourth cesarean to get a baby out, on average, then you can only imagine what kind of maternal damage you're going to do, or what kind of delay you're going toincur, trying to get that baby out that really needs to come out within about 5.

Julia Johnson, MD: Clearly, we need some research in this area to look at the effect on newborns of repeat cesarean section and adhesion formation.

Wright Bates, MD: We were surprised to find that this delay occurred regardless of the experience of the surgeon, and it also occurred whether it was a scheduled C-section or an emergent C-section. We didn't have any patients who were having their fourth repeat emergently, thankfully. But the indication and the experience of the surgeon did not matter. It still took longer if there were multiple repeats and if adhesions were present.

Michael Diamond, MD: Other than repeat cesarean sections or multiple repeat cesarean sections, are there other factors which increase the risk of adhesion development after cesarean section?

Deirdre Lyell, MD: We looked at anything that could potentially be predictive, and we found that patients who were receiving public assistance had a 5-fold increase overall in the rate of adhesions, independent of all other factors and independent of the type of surgical closure, the type of sutures used, anything else -- infection, labor, anything -- a 5-fold increase based on just receipt of public assistance.

Michael Diamond, MD: What are some of the approaches that we can try to utilize to try to reduce adhesion development after cesarean sections?

Julia Johnson, MD: Unfortunately, there is very little evidence regarding lessening the risk of adhesion formation at cesarean section. But we do know about ways of lowering the risk with surgery, laparotomy in general. We can look to those guidelines in minimizing adhesion formation. There is also some evidence in terms of the closure of the rectus muscle and the parietal peritoneum that can be useful for surgeons when they are doing initial cesarean sections. I think your study, Dr. Lyell, showed that, indeed, there is some evidence that the way we do the closure has an impact on adhesion formation.

Deirdre Lyell, MD: Absolutely. I think that really goes to the point that what is applicable to gynecologic surgery and what we know to be true with regard to adhesion formation does not necessarily translate to cesarean deliveries. For example, we studied this question of whether or not closing the peritoneum would protect against adhesions. In gynecologic surgery and general surgery, it is generally believed that you leave the peritoneum open to reduce tissue ischemia, and reduce the incidence of adhesions. We conducted a prospective cohort study of 172 patients and looked at adhesion scores that were determined by surgeons at the time of first repeat cesarean, and to our surprise we found that closing the peritoneum was actually significantly protective against adhesions. Overall the odds ratio was 0.2, it was a four-fifths reduction in adhesions if you close the peritoneum, for dense and filmy adhesions. For dense-alone adhesions, we found that closing theperitoneum actually conferred about a two-thirds reduction in the risk of forming dense adhesions at the first follow-up cesarean. When we calculated the number needed to treat, we found that for every 10 cesareans that you performed, if you closed the parietal peritoneum in all 10 patients, 2 fewer patients will have adhesions at repeat cesarean.

Julia Johnson, MD: That changes our standard of care in terms of the way that we do cesarean sections.

Deirdre Lyell, MD: I think we need to be cautious, though. That is one study. There are other studies out there that have found slightly different outcomes, but they've often mixed in closure of the visceral peritoneum and a lot of other steps. We controlled for all that in a multilogistic regression and so I do feel very comfortable with our findings.

Michael Diamond, MD: What about 1-layer vs 2-layer closure of the uterus, any studies on the impact that has on adhesions after cesarean section?

Deirdre Lyell, MD: That's a great question. It is not in the literature. We went back to our own data set and found that actually 2-layer closure was associated with fewer bladder adhesions. It is data that aren't published, and we're actually working on getting that out into the literature now.

Michael Diamond, MD: What else can be done to lessen adhesion development?

Julia Johnson, MD: That is a good question. I think there is clear information that giving gentle tissue handling; having meticulous hemostasis; being sure to excise any necrotic tissue; minimizing ischemia; and making sure that we use nonreactive suture material; also preventing a foreign body reaction; and very important -- certainly in cesarean section -- lessening the risk of postoperative infection. Those are the standards we use as OB/GYNs for our gynecologic surgery. Those have been well-delineated in the ASRM practice guidelines which were first published in July of '07 and more recently put out again in November of '08 -- for those who want to reference that material. We also can think about the use of barriers.

Julia Johnson, MD: Certainly adhesion barriers are available. They have been shown in gynecologic procedures to lessen the risk of adhesion formation. We know, for example, with a myomectomy that 90% of women who have this surgery will have adhesion formation. The use of barriers has been documented to have some value in lessening the risk of adhesion formation after gynecologic procedures.

Michael Diamond, MD: What about the use of these agents after cesarean section?

Wright Bates, MD: The data is limited, and there is one case series, from a single investigator. It was nonrandomized and retrospective in nature, but reassuring in that 52 patients were examined at repeat C-section, 27% had had an adhesion barrier -- in this case Seprafilm placed previously -- and in 25% nothing was done. Then they went back and looked at the incidence of adhesions and -- similar to our study -- looked at time to deliver the baby. If a barrier had been used, only 7.4% of the patients, or 2 out of 27, actually had adhesions; in those who they used nothing, that they just did their standard techniques, almost half. It is interesting to note that that number falls right in the range with our own data, as well as close to what you saw. Clearly, use of a barrier in their series reduced adhesions.

They also looked at time to deliver the baby, and this group was very fast, I might add -- or we were slow, depending on your perspective -- but in the group where a barrier was used, it took 5.7 minutes to deliver the baby. In those that they used nothing, it took 7.5 minutes. While you could say that 2 or 3 minutes is not a big deal, I know you've been in cases where 2 minutes is an eternity.

Deirdre Lyell, MD: Absolutely.

Wright Bates, MD: Then finally they looked at the total time to procedure, and it was about 39 minutes in those who had a barrier and more than 45 minutes in those who didn't -- anecdotal, retrospective, single operator, not controlled in a rigorous scientific fashion, but some interesting information nonetheless.

Michael Diamond, MD: Other thoughts about the use of barrier agents for reduction of adhesions?

Julia Johnson, MD: Well, certainly they have been well-documented to be beneficial for gynecologic procedures that we do, but unfortunately there is really no science to aid with our decision-making in terms of cesarean section. I know in my part of the country, on the east coast, I have not seen these barriers being used routinely with C-sections. Having said that, it would be very good to have some information so we can inform all of our OB/GYNs regarding the potential benefit of using these barriers.

Deirdre Lyell, MD: I do know there is a prospective randomized trial in place for at least one of the barriers.

Wright Bates, MD: I think there are some geographical differences. I do see the use increasing in the southeast, and I have heard of a large academic center in south Florida that routinely uses them. You're absolutely right. We don't have good randomized data, but I think it's a concern we all have: What should we be doing?

Michael Diamond, MD: Perhaps each of you would like to give us a final thought or two to finish up our panel discussion. Dr. Johnson?

Julia Johnson, MD: Well, indeed, with the increased number of cesarean sections that are being performed, and a high percentage of patients selecting to have a repeat cesarean section, I really do think we need to think about adhesion formation. Clearly it can have adverse effects for the women involved, potentially an adverse effect on their infants, and at the very least we need to use very strident surgical techniques to lessen that risk of adhesions.

Wright Bates, MD: Absolutely. I would add that sometimes our perspective is not accurate. I do still hear surgeons of all walks of life say that their patients don't get adhesions and that adhesions don't occur, and I think the preponderance of evidence demonstrates that they are a real problem. Nine times out of 10 with major exploratory laparotomies we see adhesions, and the literature would say somewhere between a third of the time and 3 out of 4 times -- as your data indicated -- adhesions are a real issue. We need to be aware of them and be looking for modalities to prevent them. I'll be the first to admit there is no perfect [prevention]. We need a barrier that is easy to apply, that has no immune reaction, and that is not permanent -- it dissolves after its job is done. More research is needed and we're looking for the panacea.

Michael Diamond, MD: Dr. Lyell?

Deirdre Lyell, MD: I would absolutely agree that more research is needed. Many of us have a lot of concerns about that 31%, with a cesarean delivery rate that high. This has become and will continue to become a major public health issue. It's only a matter of time until we start to see more maternal morbidities, many of them adhesion-related. Often they're placental-related, but I think adhesions in this setting are really under-appreciated -- many more maternal morbidities and also many more fetal and neonatal morbidities directly as a result of adhesions. When you look at this as the most common surgical procedure performed in the United States, it is really shocking the dearth of data that we have in terms of how to best perform this. The data that we have so far, I think what we can extrapolate is knowledge of -- as Dr. Johnson has said -- good tissue handling, good surgical technique. Good surgical technique is critical, but also we need better data on what todo with the rectus muscles, what to do with the peritoneum in a prospective form, whether or not adhesion barriers will help. Hopefully in the years to come we will see prospective randomized studies in this area.

Michael Diamond, MD: I would like to conclude by thanking Dr. Bates and Dr. Lyell for their studies, which I think helped us illustrate just how often adhesions are occurring after cesarean section. It is something I hadn't previously fully appreciated. While I think that may be a function of different surgical techniques now as compared to prior times, nonetheless I think it raises a critical issue, particularly now that we're having over a million cesarean sections a year in this country. There are a number of issues that have come up during our discussion today which I think are critical for some of those future studies -- type of uterine closure, peritoneal closure, type of cesarean section incisions -- all of which may very much have an impact on the likelihood of adhesion development. The question will be, what can we do to reduce them in this population in order to minimize the potential adverse outcomes which have been suggested by your studies, and tobetter document those so we know what it is we need to address and minimize.

Once again, I'd like to thank you all for your participation today, Dr. Johnson, Dr. Bates, Dr. Lyell, and Medscape for sponsoring this educational activity.

This activity is supported by an independent educational grant from Genzyme.