Background
Surgical site infections after cesarean delivery are a cause of maternal morbidity and are typically caused by skin microbial flora. Preadmission application of chlorhexidine gluconate using impregnated cloths may decrease surgical site infections by decreasing the abundance of microbial flora.
Objective
To determine whether the application of chlorhexidine gluconate cloths the night before and the morning of scheduled cesarean delivery decreases the risk of surgical site infections by 6 weeks postoperatively compared with placebo.
Study Design
In this single-center, double-blind, placebo-controlled trial, patients were randomized (1:1) to receive either Sage 2% chlorhexidine cloths or Sage Comfort Bath fragrance-free cloths (placebo) to apply to 6 skin sites on the body (neck, shoulders and chest, armpits, arm and hands, abdomen and groin, left leg and foot, right leg and foot, back and buttocks) the night before and after a shower the morning of scheduled cesarean delivery. Routine clinical and operative procedures were followed. The primary outcome was surgical site infections (superficial or deep incisional with or without organ space endometritis) by 6 weeks after cesarean delivery. The secondary outcomes were surgical site infections by 2 weeks and other wound-related complications by 2 and 6 weeks after cesarean delivery.
Results
From April 2015 to August 2019, 1356 patients were enrolled: 682 were assigned to the chlorhexidine group and 674 to the placebo group. The groups were similar in demographic and medical characteristics. A total of 14 patients were lost to follow-up before cesarean delivery (10 in chlorhexidine and 4 in placebo) and 33 were lost to follow-up after cesarean delivery (10 in chlorhexidine and 23 in placebo). Among the remaining 1309 (97%), no difference was found in surgical site infections by 6 weeks between the 2 groups (2.6% in chlorhexidine vs 3.7% in placebo; P =.24). There were no differences in secondary outcomes at 2 or 6 weeks and no differences in primary outcome in a per-protocol analysis.
Conclusion
Preadmission use of chlorhexidine gluconate cloths compared with placebo does not reduce the risk of surgical site infection after scheduled cesarean deliveries. Following the standard of care guidelines results in a low risk of surgical site infections in this group of patients.
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Cesarean deliveries are the most frequently performed inpatient surgeries in the United States, with a growing proportion that are planned. Although cesarean delivery can be lifesaving for the mother and fetus, it is not without risks including postoperative surgical site infection (SSI). The rate of postoperative SSI after cesarean delivery is between 3% and 18%. Women who experience an SSI after cesarean delivery experience substantial morbidity, such as increased length of hospital stay, hospital readmission, pain, delay in returning to normal activities, and depression, and often must pay additional healthcare costs. Interventions to reduce SSI after cesarean delivery are important to ensure the health of the new mother and promote healthy mother-infant bonding.
Why was this study conducted?
To determine whether the application of chlorhexidine gluconate cloths, a topical skin antiseptic, before scheduled cesarean deliveries decreases the rate of surgical site infection.
Key findings
Compared with placebo, chlorhexidine gluconate cloths did not reduce the rate of surgical site infections after cesarean delivery.
What does this add to what is known?
This study does not support the preadmission use of chlorhexidine gluconate cloths to reduce surgical site infection for scheduled cesarean deliveries.
Native skin microbial flora is the most common pathogen causing SSI after surgical procedures including cesarean delivery. In general, the most commonly isolated pathogens responsible for SSIs are Staphylococcus aureus , Enterococci , Pseudomonas aeruginosa , Escherichia coli , Streptococci , Enterobacter species, Proteus species, Klebsiella pneumoniae , and Serratia species. Thus, strategies to reduce skin microbial flora load have been a focus of SSI prevention intervention. The routine use of systemic antibiotic prophylaxis directed against these microorganisms has been effective in reducing the incidence of postcesarean infections. Systemic antibiotics directed against a wider range of pathogens, such as ureaplasma and others, have further reduced the incidence of postcesarean SSI. ,
Additional interventions and techniques have been proposed and evaluated, such as wound closure techniques and skin preparation. , Chlorhexidine gluconate (CHG) has excellent potential to reduce SSIs, because it has a broad-spectrum activity against gram-positive and gram-negative organisms, including methicillin-resistant S aureus which tends to be a common cause of SSIs. A randomized trial found the superiority of chlorhexidine-alcohol over iodine-alcohol preoperative skin antiseptic solution in patients receiving systemic antibiotic prophylaxis for reduction of SSI after cesarean delivery. Preincision chlorhexidine-alcohol solution is a commonly used skin preparation before performing cesarean deliveries.
One approach for additional preoperative antiseptic use of CHG has been preoperative bathing or showering with CHG soap or solution. However, most studies that evaluated this approach have not found a decrease in SSI. , Another approach for preoperative use of CHG is the application of CHG using impregnated cloths applied to the skin done by patients at home before surgery. The CHG solution then dries on the skin and is not washed off. Several studies in the orthopedic literature that evaluated the use of patient-administered, preoperative CHG cloths have found a decreased rate of SSI infection. Its effectiveness has never been studied in women undergoing scheduled cesarean delivery.
We conducted a double-blind, randomized, placebo-controlled trial to determine whether preoperative application of CHG the night before and the morning of planned cesarean deliveries would decrease SSI by 6 weeks after surgery.
Materials and Methods
This study was conducted at the Mount Sinai Hospital, a single tertiary referral center. The trial protocol was approved by the Icahn School of Medicine Institutional Review Board. The study was registered in ClinicalTrials.gov (NCT2402907). Women aged 18 years or older who were at >24 weeks’ gestation, scheduled for a primary or repeat cesarean delivery, and willing and able to provide informed consent in English or Spanish were eligible. Women who had an allergy to chlorhexidine or an unplanned or emergency cesarean delivery were excluded. Recruitment occurred between April 2015 and August 2019.
Participants were randomly assigned in a 1:1 ratio to the intervention or control group using a block randomization. A total of 70 boxes were prepared with 20 envelopes containing instructions and cloths; 10 with CHG cloths and 10 with placebo cloths. Upon enrollment, an envelope was pulled from the first box and the materials were provided to the participant. A replacement envelope was pulled from the second box and placed in the first box. The second box provided the replacement envelopes until it was empty. Then, a third box provided the replacement envelopes and so on. This method tied randomization to the distribution of material and assured a 1:1 ratio. The boxes with the sealed envelopes were kept in the Labor and Delivery triage room.
The envelopes provided to the participants contained instructions and a diagram indicating correct application of the cloths and 6 sealed packages containing 2 cloths each. Participants were instructed to apply the cloths as directed on the night before the surgery. Participants were also instructed to shower in the morning of the scheduled surgery and use 6 cloths approximately 3 hours before the scheduled cesarean delivery. Patients received a phone call, text message, or email reminder the night before surgery to apply the cloths. Participants were encouraged to bring the empty packages to confirm adherence.
All distributed cloths were made of polyester. Participants in the intervention arm received CHG cloths. The CHG cloths included the active ingredient of 2% CHG and the inactive ingredients aloe vera, dimethicone, glucono delta-lactone, glycerin, Igepal, polysorbate 20, propylene glycol, and USP purified water. The participants in the placebo arm received a cloth impregnated with purified water, methylpropanediol, glycerin, tetrasodium glutamate diacetate, decyl glucoside, phenoxyethanol polysorbate 20, citric acid, benzoic acid, dehydroacetic acid, ethylhexylglycerin, simethicone, tocopheryl acetate, vitamin E, and Aloe barbadensis leaf. The ingredients in the placebo cloths include a preservative system consisting of inactive ingredients that are not intended to provide bactericidal effects on the patient’s skin.
Sage Products LLC, a business unit of Stryker (Kalamazoo, Michigan), provided the intervention and placebo cloths but did not provide any funding or participate in the study design, conduct of the study, analysis, or reporting of the trial. The packages containing the cloths were labeled with a 4-digit number indicating the product. Only Stryker was aware of group assignment. Patients, recruiters, principal investigators, and statisticians were blinded to the study groups.
All standard procedures were followed for the cesarean delivery such as use of preoperative antibiotic and immediate preoperative chlorhexidine-alcohol skin preparation. At our institution, cefazolin is the preoperative antibiotic of choice, but clindamycin or vancomycin is used for patients with a severe allergy to penicillin. Prophylactic antibiotics were administered within 1 hour of the surgery. Suture material and skin closure were per provider preference.
As per standard of care of patients after cesarean delivery, the study participants were evaluated at approximately 2 weeks and 6 weeks by their providers. Patients were examined at additional visits as needed.
The primary outcome was the rate of SSI (superficial and deep incisional and organ space) by 6 weeks after the procedure. At study design, SSI was defined by the Centers for Disease Control and Prevention (CDC) criteria ( Supplemental Table 1 ). , Endometritis was included as a primary outcome because it met the criteria for an organ space SSI. Secondary outcomes included erythema at the operative site, skin separation, drainage, fever, hematoma, seroma, hospital readmission for wound complications, and length of index hospital stay by 6 weeks after cesarean delivery and SSI, erythema at the operative site, skin separation, drainage, fever, hematoma, and seroma by 2 weeks after cesarean delivery.
Trained study coordinators reviewed patient electronic health records to obtain primary and secondary outcome data. In addition, data was collected on demographic characteristics (maternal age, gestational age at delivery, body mass index at delivery, race, ethnicity, type of insurance), medical history (presence of chronic hypertension, pregestational diabetes, asthma), obstetrical history of the index pregnancy (primiparity, repeat cesarean delivery, gestational hypertension, gestational diabetes, preeclampsia, cholestasis), and operative characteristics of cesarean delivery (estimated blood loss, length of procedure, preincision prophylactic antibiotics, type of skin closure). In addition, patients were contacted at 2 weeks and 6 weeks by study coordinators and information on any SSI-related or other complications was ascertained. Information obtained included confirmation of outcomes, such as any wound complications, hospital readmissions, need for outpatient antibiotics for wound infection, drainage from incision, and any other postoperative complications.
All study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at the Icahn School of Medicine at Mount Sinai. REDCap is a secure, web-based software platform designed to support data capture for research studies. The study complied with the CONSORT guidelines for reporting randomized trials and the checklist was used to ensure compliance.
Statistical analysis
The original design of this study included a sample size of 1000 patients that ensured approximately 88% power to detect a 67% reduction in SSI and endometritis from an assumed rate of 6% in the control group using a 2-sided, 0.05-level test and assuming a 7% drop out rate. A 6% rate of SSI was based on an internal review of data from the Mount Sinai Hospital from October 2013 to December 2013 that found that the rate of SSI after cesarean delivery was 6.3% (34/543). This rate was calculated for all cesarean delivery patients because the query tool was unable to distinguish between planned and unplanned cesarean deliveries. A monitoring report revealed a higher than expected rate of nonadherence; hence the sample size was increased to 1356 participants. This sample size ensured 80% power to detect a 67% reduction in SSI from an assumed SSI rate of 6% in the control group using a 2-sided, 0.05-level test and assuming a 20% nonadherence rate and 5% dropout.
The primary outcome was compared by randomization assignment using a 0.05-level chi-square test. Secondary outcomes were compared using chi-square or Fisher’s exact test for categorical measures and t-tests or Mann–Whitney U tests for continuous measures, as appropriate. Exploratory stratified analyses of the primary outcome were conducted by obesity, maternal medical conditions, preoperative antibiotics, skin-closure type, and postpartum hemorrhage. The relative risk (RR) of the primary outcome for patients randomized to CHG vs placebo and the corresponding 95% confidence intervals (CIs) are reported for each stratum. A per-protocol analysis of the primary outcome and secondary outcomes after 6 weeks was also conducted, restricting the patient sample to those who applied cloths both the evening and morning before their procedure. SAS version 9.4 (SAS Institute Inc, Cary, North Carolina) was used for all analyses.
Results
From April 2015 to August 2019, 1568 patients were assessed for eligibility. Of the 1568 patients, 212 declined participation and 1356 patients were enrolled ( Figure 1 ). Of the 1356, 682 were randomized to the CHG group and 674 to the placebo group. Among the 1356 randomized patients, 14 were lost before the procedure (10 in the CHG group and 4 in the placebo group) because of vaginal delivery (12) or delivery at an outside institution (2).
A total of 1342 underwent cesarean delivery at the Mount Sinai Hospital, 672 in the CHG group and 670 in the placebo group. Of the 672 in the CHG group, 10 did not return for their 6-week visit, and of the 670 in the placebo group, 23 did not return for their 6-week visit. Of the initial 1356 randomized women, primary outcome data was available for 1309 (97%) (662 in the CHG group and 647 in the placebo group).
No significant differences were found between the groups in baseline characteristics ( Table 1 ), except for asthma that was more common in the CHG group (6.9% vs 4.2%, P =.03).
| Characteristic | Chlorhexidine n=682 | Placebo n=674 |
|---|---|---|
| Demographic data a | ||
| Maternal age (y) (mean±SD) | 35.1±5.0 | 35.1±5.0 |
| Gestational age at delivery (wk) b | 38.7±1.2 | 38.8±1.3 |
| Body mass index at delivery (kg/m 2 ) b | 30.1±5.9 | 30.2±5.4 |
| Race, n (%) | ||
| White | 436/569 (76.6) | 416/553 (75.2) |
| Black | 66/569 (11.6) | 60/553 (10.8) |
| Other | 67/569 (11.8) | 77/553 (13.9) |
| Ethnicity: Hispanic/Latina, n (%) | 118/662 (17.8) | 102/647 (15.8) |
| Private insurance, n (%) | 604 (88.6) | 577 (85.6) |
| Medical history a , n (%) | ||
| Chronic hypertension | 23 (3.4) | 26 (3.9) |
| Pregestational diabetes | 9 (1.3) | 13 (1.9) |
| Asthma | 47 (6.9) | 28 (4.2) |
| Obstetrical history a , n (%) | ||
| Primiparous | 248 (36.4) | 236 (35.0) |
| Repeat cesarean delivery | 387/681 (56.8) | 394/673 (58.5) |
| Gestational hypertension | 17 (2.5) | 18 (2.7) |
| Gestational diabetes | 69 (10.1) | 57 (8.5) |
| Preeclampsia | 8 (1.2) | 13 (1.9) |
| Cholestasis | 8 (1.2) | 7 (1.0) |
| Operative characteristics a | N= 672 c | N=670 c |
| Estimated blood loss (mL) (median, IQR) | 719.5 (479.5, 800.0) | 717.5 (484.0, 800) |
| Length of procedure (min) (median, IQR) b | 62.0 (53.0, 74.0) | 62.0 (53.0, 76.0) |
| Preincision prophylactic antibiotics | ||
| Clindamycin/gentamicin | 14/659 (2.1) | 12/660 (1.8) |
| Cefazolin | 645/659 (97.9) | 648/660 (98.2) |
| Skin closure type | ||
| Staples | 56/672 (8.3) | 58/670 (8.7) |
| Subcuticular suture | 616/672 (91.7) | 612/670 (91.3) |
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