Tweetable abstract
Currently, there is no conclusive consensus regarding usage of adhesion barriers at cesarean section. Previous studies of HA-CMC were performed by different surgeons which affect background adhesion incidence, and studies of ORC were limited to one small study. We are interested in the adhesion rates under the minimal effect of confounding factors and the postoperative outcome of different adhesion barriers. We found the use of adhesion barrier at cesarean delivery didn’t improve adhesion formation but had significantly higher rates of postcesarean fever. Our result does not support application of anti-adhesion films during cesarean deliveries especiallyin emergency cesarean section or in a woman having labor before operation.
Introduction
Repeat cesarean section (CS) has led to more difficult surgeries, secondary to adhesion found at delivery. The more often the abdomen is entered, the more extensive and dense adhesion may be encountered. Previous research reported prevalence of adhesion in 11.5–46% of women at their second CS and 26–75% of women during their third CS [1-11]. Adhesion has been linked in the delayed delivery of the neonate, higher incidence of bladder or bowel injury, excessive bleeding, and increased operative time during repeat CS [10-13]. There are several adhesion prevention barriers approved by the U.S. Food and Drug Administration (FDA) for the prevention of postoperative adhesion. Two commercially available barriers for CS such as HA-CMC (Seprafilm®) or ORC (Interceed®) have been studied, and some retrospective and prospective studies suggest that these barriers reduce the amount and severity of adhesion formation and blood loss [14-21]. In our experience, adhesion after the primary CS is generally minimal or nonexistent. One randomized trial and two retrospective researches demonstrated that HA-CMC applied during CS did not reduce adhesion formation and affect operative outcome at repeat CS [22-24]. However, these studies of HA-CMC reported the data were from a multicenter and CS were performed by different surgeons with varying experience and surgical techniques (e.g., rectus muscle approximation, uterine or peritoneal closure, packing the gutters) [3, 4, 25-30]. Second, they did not exclude the patient with history of uterine incision or laparoscopy. These confounding factors affect background adhesion incidence. Third, data regarding the use of ORC for adhesion prevention during CS were limited to one small study. So we executed a CS retrospective chart review performed by three physicians with profound experience and similar surgical techniques. We evaluated clinical efficacy of placement of the HA-CMC and ORC during primary CS and assess surgical outcomes at primary and secondary CS.
Patients and Methods
We conducted a retrospective study between January1, 2011, and September 31, 2019. The study was reviewed and approved by the institutional ethics committee of the MacKay Memorial Hospital (18MMHIS155e). The study included all Asian women undergoing primary CS performed by the three experienced surgeons (at least more than 20 years as an obstetrician) at MacKay Memorial Hospital, a quaternary care referral hospital at Taipei. Most patients received secondary CS by the same surgeon, while a minority received the secondary operation by the other two surgeons at or less than five years interval. Additional inclusion criteria included the following: both deliveries were live neonates at 23–42 weeks of gestation, delivered through Pfannenstiel incisions, intraperitoneal CS, and both hysterotomy with low transverse incision. Exclusion criteria included the following: (a) American Society of Anesthesiologists (ASA) score >3; (b) medical records mentioning history of pelvic inflammatory disease or endometriosis; (c) uterine incision (e.g., myomectomy, cesarean), open abdominal or laparoscopic pelvic surgery before the primary or the secondary CS; (d) tubal sterilization, ovarian cystectomy or myomectomy during CS.
Operative notes and electronic medical records on labor and delivery of patients concerning the primary and the secondary surgical procedures were used to obtain data on demographic data (maternal age, parity, gestational age, body mass index (BMI), ASA score) and relevant data from their medical and surgical history. We also collected the basic characteristics and complications at each surgery, including preoperative and postoperative laboratory data, estimated blood loss, visceral organ injury, the description of adhesion, operative times, and skin-to-delivery time.
Adhesion reduction agent in CS is the indication of HA-CMC or ORC in Taiwan. Our pregnant women could choose to use anti-adhesion material or not before undergoing operation. Preoperative skin preparation was done and prophylactic and therapeutic antibiotics were given according to local standards. After delivery, all uterus were closed in two layers, and closure of the bladder flap and peritoneum and rectus muscle approximation were also done. Abdominal irrigation or packing of bowel was avoided during operation. HA-CMC or ORC was placed over the incisional site and the midline anterior surface of the uterus. This was usually completed with 1 sheet or cut into smaller pieces to facilitate placement. Because there has not been a validated adhesion scoring system to be used for cesarean deliveries, we evaluated adhesion that was in the field of manipulation. Adhesion was scored as severe or mild, if the operative summary contained the words severe ,extensive , vascular , and dense or if the operative notes used words such as mild , few , filmy, andsome . The outcome measures were the incidence of adhesion, skin-to-delivery time (defined as the time from skin incision to the first neonate delivery), operative time (defined as the time from skin incision to skin closure) during the secondary CS, estimated blood loss, and rates of intraoperative (e.g., bladder or bowel injury, hysterectomy, injury to uterine vessels, postpartum hemorrhage, or drop of Hb) and postoperative complications (e.g., fever, ileus, incisional wound infection, metritis, UTI, hospital length, readmission for SSI, and the frequency of postpartum clinic visits) related to the repeat CS. We also examine the short-term postoperative outcome (as repeat CS) of the adhesion barriers placement at the primary CS as measured by postoperative complications (e.g., postoperative white blood cell count).
Sample size at each group was calculated based on studies performed by Fushiki et al. [16] and Chapa et al. [19] for the endpoint of adhesion formation. We estimated that a minimum of 20 patients in HA-CMC group and 14 patients in ORC group would be required to detect these differences with 80% power.
Statistical analysis was performed with R software, version 3.3.1 (R Project for Statistical Computing, Vienna, Austria). Differences in demographics among the three groups were assessed with the Student’st- test or chi-square as appropriate and the results for continuous variables were given as the mean ± SD. Multiple logistic regression was used to evaluate for SSI risk factors of postcesarean fever at the primary CS. An interaction term analysis was performed to examine the impact of SSI risk factors and use of adhesion barrier on postcesarean fever rates at the primary CS. The magnitude of statistical significance was expressed with Adj-HR and 95% CI. Statistical significance was defined at the 95% level (P<0.05).
Results
A total of 236 patients were included in this study and 37 were excluded due to one or more exclusion criteria. Finally, 99 women received the HA-CMC, 26 women received the ORC, and 74 did not receive adhesion barrier at the primary CS. There were no differences in patient demographics or preoperative characteristics at the time of the primary CS except for gestational age and preoperative white blood cell count, which was highest in the nonuser group (Table 1). Table 2 shows intraoperative characteristics including skin-to-delivery time, total operative time, adhesion condition, intraoperative complications or estimated blood loss, and neonatal birth weight, and there were no significant differences among the 3 groups. It also contained postoperative laboratory data includinghematocrit, drops of hematocrit and white blood cell count, with no significant difference among the groups. Similarly, there were no differences in the need of additional therapeutic antibiotic, hospital length, readmission for SSI, and the frequency of postpartum clinic visits. However, two patients who received the HA-CMC adhesion barrier were readmitted to the hospital for postpartum metritis. But both groups that used adhesion barrier had significantly higher rates of postoperative fever compared with the control group (HA-CMC 17.2% vs. ORC 15.4% vs. nonuse 5.4%,p =0.045).
Demographic data at the time of the secondary CS are shown in Table 3. There were no significant differences among the groups except for gestational age and the percentage of adhesion barrier use at the secondary CS. Around 63% of nonuser at the primary CS chose to use adhesion barrier at the secondary CS and 97% and 96.2% of the other two groups chose to use adhesion barrier at repeat CS. There were less than 40% of patients in labor and less than 20% of patients with membrane rupture before operation in either group at secondary CS, while there were50–70% of patients in labor and 40–60% with membrane rupture before the primary CS. Table 4 shows adhesion and intraoperative and postoperative outcomes at the secondary CS. Notably, there were no differences as regards skin-to-delivery time, total operative time, adhesion formation, bladder or bowel injury, hysterectomy, injury to uterine vessels, estimated blood loss, or drop of Hb.
Since the use of adhesion barrier user at the primary CS had significantly higher rates of postcesarean fever, the following SSI risk factors relating to postcesarean fever were evaluated using logistic regression: use of the adhesion barrier, labor or membrane rupture before operation, emergency operation, total operative time, estimated blood loss ≧500 cc, BMI ≧30 kg/m2, diabetes mellitus, hypertension, or preeclampsia. All nine risk factors were entered in a multiple regression and we found the use of adhesion barrier at the primary CS as an independent risk factor of postcesarean fever (p= 0.045, Adj-HR=3.53, 95% CI=1.03–10.24) (Table 5). An interaction term analysis was performed to examine the impact of SSI risk factors and use of adhesion barrier on postcesarean fever at the primary CS (Table 6). The strongest risk factor for postcesarean fever is the use of anti-adhesion filmduring emergency CS (p= 0.041). Borderline interaction between labor before operation and use of anti-adhesion filmmay play some role for postcesarean fever (p= 0.054).In the subgroup of labor before operation and emergency CS, adhesion barrier use had significantly higher risk of postcesarean fever (labor before operation: user 21.2% vs. nonuser 2.2%,p= 0.018, Adj-HR=12.12, 95% CI=1.53–95.78; emergency CS: user 20.3% vs. nonuser 2.0%, p= 0.016, Adj-HR=12.71, 95% CI=1.62–99.62).