More than 28 million surgical procedures are performed annually in the United States.1 A common infection in patients undergoing surgery is surgical-site infection, accounting for 14–16% of all hospital-acquired infections2 and 38% of nosocomial infections among surgical patients.3 Surgical-site infection extends length of hospital stay by 9.7 days and increases cost by $20,842 per admission.4 On the national level, surgical-site infection costs an additional 406,730 hospital-days and $991 million in incremental hospital costs annually.4 Patients with surgical-site infection are twice more likely to die during their hospitalizations than those without such infections.5
Concerns about morbidity, mortality, and the financial burden of surgical-site infections have led to advances in infection control practices, including improvements in operating room ventilation, sterilization methods, surgical techniques, and the availability of antimicrobial prophylaxis. Based on the Centers for Disease Control and Prevention (CDC) recommendation,6 2% chlorhexidine-based preparations should be used to cleanse the insertion site of vascular catheters. However, neither the CDC nor the American College of Obstetricians and Gynecologists have issued a recommendation regarding which antiseptics should be used preoperatively to prevent postoperative surgical-site infections.
Studies examining the efficacy of antiseptics in preventing surgical-site infections have shown inconsistent results, ranging from fewer surgical-site infection with chlorhexidine use compared with iodine7–10 to a slight increase in surgical-site infection with chlorhexidine use11 to no difference.12 Darouiche et al,9 in a recent randomized controlled trial on the topic, showed a 41% reduction in surgical-site infection with chlorhexidine-alcohol as compared with aqueous iodine use (P=.004). This result was later confirmed in a meta-analysis10 in which a 32% reduction in surgical-site infection was shown with the use of chlorhexidine-alcohol.
Regarding gynecologic patients, superiority of chlorhexidine to povidone iodine also has been shown among patients undergoing vaginal hysterectomy7 or women undergoing elective gynecologic laparotomies.13 However, examining the literature, no data are available addressing the benefits of chlorhexidine compared with povidone-iodine among women undergoing cesarean deliveries. Surgical-site infection is shown to be more common in planned cesarean delivery than planned vaginal births.14 Overall, rate of surgical-site infection is reported to range from 2.71% in low-risk to 7.53% in high-risk cesarean delivery patients, with a mean of 3.15%.15 However, cesarean delivery is considered a clean contaminated surgery, thus incorporating different types of pathogens. Furthermore, many women who undergo this procedure are young and may lack the traditional risk factors for surgical-site infection, such as older age or smoking. Whether rate of surgical-site infections among cesarean delivery patients differs by antiseptic type is currently unknown. With nearly 1.4 million cesarean deliveries performed annually in the United States (32% of all births),16 efforts at reducing surgical-site infections in this population is a top public health priority.
Because of the paucity of data, the present study was undertaken with a primary aim of comparing the efficacy of chlorhexidine-alcohol with povidone-iodine in preventing surgical-site infections in cesarean deliveries. Overall, lack of sufficient data concerning superiority of chlorhexidine in prevention of surgical-site infection and need for additional research in this area have been emphasized by others.17
MATERIALS AND METHODS
After receiving institutional review board approval at Baylor College of Medicine and the Harris County Hospital District (protocol number H-27918), we conducted a retrospective cohort analysis of 1,000 successive participants who underwent cesarean delivery at Ben Taub General Hospital, Houston, Texas, over a 1-year study interval between August 2009 and August 2010. Our time interval reflected the 500 consecutive cases immediately before and the 500 consecutive cases immediately after preoperative skin cleansing protocol changes. Specifically, an aqueous solution of 10% povidone-iodine was used exclusively as preoperative skin cleansing agent before February 2010 at the study institution. From February 2012 onward, a protocol adopted and approved by the institution and service resulted in a uniform change to chlorhexidine-alcohol. No alterations in attending physicians or residents were made during the entirety of the 1,000 case-participant interval (mid-year protocol change).
For purposes of this study, we reviewed charts of 500 successive women undergoing cesarean delivery immediately before February 2010, when povidone-iodine was in use, and 500 such deliveries immediately after that date, when chlorhexidine-alcohol was alternately applied; all cases were successive, and exclusion and inclusion criteria were unchanged over the 1,000 case-participant interval. Data abstraction was performed by the research team, supervised by the primary author. Review of these 1,000 consecutive cesarean deliveries allowed identification of all cases of surgical-site infection during a specific time period. Receipt of chlorhexidine or iodine was abstracted and verified from the patient records, including operative reports, nursing records, and anesthesia reports. The concentration of chlorhexidine used is 2% chlorhexidine gluconate with 70% isopropyl alcohol. Both chlorhexidine-alcohol and povidone-iodine were applied to the surgical field with rubbing or painting. Within 30 minutes of surgery, patients received the preincisional antibiotic (cefazolin [Ancef]) unless they had an allergy to cephaloporins. This latter group (n=13) received antibiotics other than cefazolin, such as clindamycin, gentamycin, or ampicillin. Patients 18 years of age or older who were undergoing cesarean deliveries and had no history of allergy to chlorhexidine, alcohol, or iodophors were eligible for enrollment. Exclusion criteria included documented concomitant infections and failure to follow-up within 4 weeks postsurgery (ie, women had to have attended their postpartum visit or have a postoperative visit documented within 30 days of delivery). Specifically, we excluded women with chorioamnionitis, pyelonephritis, urinary tract infection, and mastitis (10 patients excluded from povidone-iodine and 13 from chlorhexidine group). Another 11 patients from povidone-iodine group and 14 from chlrohexidine group were excluded because of incomplete follow-up outcome data.
As per routine protocol, preoperative evaluation of patients included medical history taking, physical examination, and routine hematologic laboratory tests. The surgical site and participant's vital signs were assessed at least once per day during hospitalization, on discharge, at the time of follow-up evaluation in the clinic or if the participant presented to emergency department with findings concerning for surgical-site infection.
The study's primary end point was the occurrence of any surgical-site infection within 30 days after surgery (CDC criterion). We examined the occurrence of individual types of surgical-site infections, specifically incisional infection or visceral or peritoneal infection. The latter consisted of any visceral organ or peritoneal, preperitoneal, or retroperitoneal space other than the incised layer of body wall that was opened or manipulated during the operation. Other abstracted information included age, BMI, gravidity, parity, gestational diabetes, smoking, remote infection (such as upper respiratory tract or sinus infection), altered immunity, previous abdominal surgery, type of skin incision (Pfannenstiel compared with vertical compared with Maylard), closure of skin incision and subcutaneous tissue, use of drains, urgency and duration of surgery, and use of preoperative and postoperative antibiotics. Type of cesarean delivery was defined as scheduled (planned ahead of due date), urgent (cesarean delivery needing to be performed within the next 30 minutes), emergent (cesarean delivery needing to be performed within the next seconds to minutes), or other (ie, secondary to arrest of labor).
Estimates for samples size were based on past research9 in which we expected a 6.6% difference in surgical-site infection between the chlorhexidine-alcohol group (9.5%) and the iodine group (16.1%). To have adequate power (80%) to detect this difference, when alpha was set to 0.05, using a two-sided χ2 test, 500 patients in each group were projected to be needed.
Characteristics between chlorhexidine and iodine users were compared via t test for continuous variables and χ2 or Fisher exact test for grouped data. Next, we assessed risk factors associated with surgical-site infection using χ2 or Fisher exact test for grouped variables and t test for continuous variables. Finally, we performed multivariable logistic regression analysis to assess the independent contribution of antiseptic type as well as other key clinical parameters to surgical-site infection. In the multivariable model, we included any variable that was associated (P<.10) with surgical-site infection and antiseptic type in univariable analysis, as well as those clinically important variables whose removal changed the effect of other factors. The final multivariable model included antiseptic type, duration of delivery, type of cesarean delivery, closure of subcutaneous tissue, type of closure of skin incision, surgeon level of training, patient age, and gestational diabetes. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated. P<.05 was considered statistically significant. All analyses were performed using the SAS System statistical system 9.3.
Mean age (±standard deviation) and parity for the entire cohort are 29.8±5.9 and 2.6±1.4, respectively. Patient characteristics by antiseptic type are presented in Table 1. As anticipated by using successive (consecutive) cases over a prescribed mid-time interval study design, participants in both study groups were similar with respect to demographic characteristics of surgeon level of training and potential comorbidities including age, BMI, gestational diabetes, smoking status, altered immunity, and antimicrobial exposure. All participants received systemic antibiotic prophylaxis within 30 minutes before incision. Method of skin incision closure was significantly different, with 91% among povidone-iodine compared with 81% among chlorhexidine using staples (P<.001). Also, fewer patients in the chlorhexidine group were classified as having undergone an urgent (29% compared with 46%; P<.001) or emergent cesarean delivery (0.6% compared with 8%; P<.001). In addition, the duration of cesarean delivery was significantly longer among the chlorhexidine-alcohol group as compared with povidone-iodine patients (67.2 compared with 60.0 minutes; P<.001). With regard to surgical-site infection, the rate was similar between the two groups (5% [n=25] chlorhexidine and 5.8% [n=29] povidone-iodine; P=.58) (Table 1). The majority (96%, n=52) of the surgical-site infections were superficial and the remaining two were organ-space, which occurred in the iodine group.
Next, we examined factors that may be associated with surgical-site infection (Table 2). In this analysis, the only factor that was significantly associated with surgical-site infection was duration of cesarean delivery; in women with development of infection, cesarean delivery lasted, on average, 10 minutes longer as compared with those who did not have development of such infection (P=.03). No other variable predicted surgical-site infection, including surgeon level of training, type of closure of skin incision, closure of subcutaneous tissue, or type of cesarean delivery (Table 2). Specifically, rate of infection was 4.8% among women with scheduled cesarean deliveries, 5.1% among urgent, 7.1% among emergent, and 6.3% among all others, including those with arrest of labor. None of these differences was significantly different (overall P=.81).
Using multivariable logistic regression modeling, we examined the independent association of antiseptic type, duration of cesarean delivery, as well as other key clinical parameters (those significantly different between the antiseptic types in univariable analysis) with surgical-site infection (Table 3). The ORs are presented for antiseptic type, duration of delivery, type of cesarean delivery, type of closure of skin incision, and closure of subcutaneous tissue, in which each variable is adjusted for all others in Table 3 as well as surgeon level of training, patient age, and gestational diabetes. In this analysis, duration of cesarean delivery remained a significant and independent predictor of surgical-site infection in which every 1-minute increase in operative time (duration of cesarean) increased the odds for infection by 1.3% (adjusted OR 1.013, 95% CI 1.004–1.022; P=.004) (Table 3). Odds for surgical-site infection remained similar between the two antiseptic types after further adjustment for all potential confounders (adjusted OR 0.74, 95% CI 0.41–1.33; P=.32). Furthermore, no other variable that was examined with multivariable modeling showed any association with surgical-site infection aside from operative time.
Comparison between studies examining the effect of antiseptic preparations on the incidence of surgical-site infection is difficult because of differences in concentration and type of solution used (alcohol compared with aqueous based). Furthermore, incidence of surgical-site infection varies by which surgical procedure is being performed,4,18 and operative time, mode of incision, and pathogen will differ. Moreover, effects of known risk factors for surgical-site infection such as older age and male gender have been shown to vary by surgical procedure.19 These variations provide the rationale for surgery type-specific studies with the aim to clarify the effect of various antiseptics on surgical-site infection by virtue of procedure performed.10
The rate of surgical-site infection observed in the current study at 5.4% is similar to that found in European cohorts of cesarean delivery patients (3.9%)20 and the reported rates in the United States (range 2.7--7.5%).15 We further found that the rate of surgical-site infection is similar regardless of antiseptic used, although there was a nonstatistically significant trend in favor of chlorhexidine (adjusted OR 0.74, 95% CI 0.41–1.33; P=.32).
This finding of a lack of significant difference is in contrast to investigations comparing the two antiseptics among other gynecologic patients.7,13 However, this discordance may be explained by differences between women and treatment standards in the present study and those in other trials. First, the participants in our study were young (mean age 29.8) and relatively healthy women undergoing cesarean delivery. By design, we excluded those with a history of congenital or acquired immune deficiency. Among our participants, less than 1% smoked; although approximately 25% had evidence of gestational diabetes, this rate was similar between the two study groups. By comparison, in the study of gynecologic surgeries by Levin et al,13 the average age was 52 and the presence of most surgical-site infection risk factors (smoking, noninsulin-dependent diabetes mellitus, hypertension) were higher among the povidone-iodine group, albeit the differences were not statistically significant. This nonsignificant difference may be secondary to small sample size in the study by Levin, because sample sizes of 145 and 111, respectively, gave 37% power to detect differences in their rates of smoking (24.6% and 16.2%) or 27% power to detect a difference in the rate of hypertension (35.9% and 27.9%) between povidone-iodine and chlorhexidine users, respectively. Culligan et al,7 examining vaginal hysterectomy patients (with mean age of 43 years), showed the superiority of chlorhexidine over povidone-iodine in decreasing bacterial colony count, a surrogate end point for infection. Similarly, in a recent study examining a comprehensive preoperative skin preparation protocol using chlorhexidine gluconate no-rinse cloths with chlorhexidine gluconate with alcohol for intraoperative skin preparation and modified instrument sterilization techniques, a significant decrease in the rate of surgical-site infection was shown.21 However, a clearly defined control group was not used and comparison was made with historical data in that study.21
The lack of superiority of chlorhexidine in our study could be attributed to our institution-specific standards and especially the uniformity of antibiotic use before incision. The significant reduction in wound infections after cesarean delivery with use of antibiotic before incision, as opposed to before cord clamping, has been previously reported.22–24 It is conceivable that in this relatively young and healthy cohort in which optimal and established measures for prevention of postpartum infections already have been undertaken, type of antiseptic may not make a significant difference in the development of surgical-site infection. Our overall rate of surgical-site infection at 5.4% is in the reported range of these infections among cesarean delivery patients in the United States (2.71--7.53%).15 The single predictor of surgical-site infection in our study was duration of surgery. This finding is consistent with evidence available in the literature in which operative duration has been reported a consistent risk factor for surgical-site infection in most surgeries.9,19,25
A limitation of the current study is lack of randomization. Furthermore, the use of a single institution in Houston, Texas, may limit generalizability of the study findings. These are balanced by our strengths in approach (consecutive cases before and after implementation of institutional protocol change) and sample size, notably the use of surgical-site infection as a primary end point in a large number of women. Furthermore, the extensive number of variables abstracted from each participant's chart for inclusion in our multivariate analysis allowed a comprehensive comparison of the two study groups on all potential confounders.
In the current era of cost containment, demonstrating the economic value of an infection control intervention is pivotal to driving its adoption as a hospital protocol. Given the significant price difference between chlorhexidine-alcohol compared with povidone-iodine ($168 compared with $52, Harris County Hospital billing services) and lack of superiority of chlorhexidine shown, it may be ill-advised to recommend chlorhexidine for surgical site antisepsis in cesarean deliveries. Our study adds evidence to the ambiguity of one universal and ideal antisepsis for all surgeries and surgical patients. The ideal method may be patient-specific and surgery-specific. This assertion needs to be investigated in future trials.
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