Surgical Drain Bacteria After Breast and Axillary Surgery
Surgical Drain Bacteria After Breast and Axillary Surgery
After approval by the Mayo Clinic Institutional Review Board, eligible subjects were recruited prospectively from the breast surgical practice at Mayo Clinic in Rochester, MN, between January 2009 and May 2011. Individuals were included if undergoing total mastectomy and/or axillary lymph node dissection for benign or malignant disease in which surgical drains were placed. Subjects were ineligible if they were pregnant, had received antibiotics within 14 days before surgery, had a known allergy to chlorhexidine, or were undergoing immediate reconstruction (because of the common use of postoperative antibiotics in this subgroup).
After informed consent, subjects were randomized to either the standard drain care regimen or the drain antisepsis regimen by a computerized randomization program, using dynamic allocation and stratifying by surgical procedure (mastectomy or lumpectomy with axillary dissection), surgeon, and body mass index (BMI <30 or >=30). In the event of bilateral procedures, patients with a unilateral cancer had sample collection and analysis from the side affected with cancer. Subjects who had bilateral cancer or bilateral prophylactic mastectomies underwent computerized randomization to select the side to be evaluated on study. The operating surgeon remained blinded to the assigned treatment arm.
All subjects received a single dose of intravenous preoperative cefazolin (dosed per weight) within 30 minutes before skin incision. In the case of cefazolin allergy, vancomycin or levofloxacin was alternate, and antibiotics were redosed intraoperatively when appropriate. A chlorhexidine/alcohol skin prep (ChloraPrep; CareFusion Corporation, San Diego, CA) or iodine/alcohol (DuraPrep; 3M, St Paul, MN) was used per surgeon preference. The surgical drainage tube used was a 15Fr round channel hubless drain secured with nonabsorbable monofilament suture. Antibiotics were not permitted beyond 24 hours after surgery. Patients could shower 48 hours after surgery, but immersion bathing was not permitted.
Study subjects and family members received personal instruction on drain care on the first postoperative day (POD) by the nurse study coordinator, and they were advised not to divulge the drain care regimen to their surgeon. All subjects in both treatment arms were instructed to strip the drain tubing, empty the bulb, and record fluid volume at least twice daily. Individuals assigned to standard drain care were also advised to cleanse the drain exit site with prepackaged 70% isopropyl alcohol wipes twice daily and to cover the drain site with a sterile gauze dressing. Subjects in the drain antisepsis arm were shown how to cleanse the drain exit site with alcohol and then apply a chlorhexidine gluconate disc dressing (Biopatch®; Johnson & Johnson Medical) at the drain site and secure it with an adherent sterile transparent occlusive dressing (Fig. 1). The chlorhexidine disc and occlusive dressing were changed every 3 days until drain removal. In addition, subjects in the drain antisepsis arm were instructed to perform antiseptic irrigation of the drainage bulb twice daily as follows: instill 10 mL of dilute Dakin's solution (0.0125% buffered sodium hypochlorite) into the drainage bulb via the exit valve (prepped with alcohol), swish occasionally over 10 minutes, and then empty and return the bulb to suction. At the time of showering, the chlorhexidine disc/occlusive dressing was left intact.
(Enlarge Image)
Figure 1.
Chlorhexidine disc dressing with occlusive adherent dressing.
If more than 1 drain was placed per surgical site (ie, 2 drains in the setting of a modified radical mastectomy), then both drains associated with that surgical site were treated according to the assigned treatment arm. Each drain associated with the surgical site was evaluated separately for bacterial colonization endpoints.
For 30 days after operation, a standardized data collection form was completed at every follow-up visit, with details including drainage volume, erythema, or skin changes at the incision and drain sites, and evidence of seroma or infection. In addition, the medical record was reviewed to screen for late infections. Blinding of the surgeon was maintained at postoperative visits by the study coordinator removing all dressing materials before surgeon evaluation. A mandatory follow-up visit occurred at 1 week (on POD 7 ± 1 day) for study cultures and for clinical evaluation for signs of infection or adverse reactions to drain antisepsis regimen. If drains were ready for removal before this, all cultures were obtained on the day of drain removal. At each visit, compliance with the antiseptic interventions was assessed by the study coordinator, who asked the subjects whether they had any difficulties that prevented completing the prescribed regimen. For patients with clinical evidence of infection, diagnostic cultures and antibiotic therapy were performed per routine clinical care. Guidelines for drain removal specified output of 30 mL or less per 24 hours for 2 consecutive days or at POD 19, whichever came first. If drain removal did not occur at the 1-week visit, then a repeat culture of drain fluid was obtained on the day of drain removal; therefore, some subjects had drain fluid cultures at 2 time points. Drain tubing cultures at removal were added to the protocol after the study was underway and are available in 76 of 100 patients.
At the 1-week visit, a 2-mL sample of drain fluid from the bulb was obtained aseptically for semiquantitative aerobic and anaerobic cultures. On the day of drain removal, cultures were obtained of both drain bulb fluid and drain tubing. Drains were removed in a sterile fashion after chlorhexidine preparation and sterile draping of the drain exit site. A 5-cm portion of the subcutaneous drain tubing was harvested, starting approximately 1 to 2 cm internal to the skin exit site.
For drain fluid culture, 1 to 2 drops of fluid were inoculated onto sheep blood, eosin methylene blue, and colistin-nalidixic acid agar plates, and anaerobic sheep blood agar plates, and 1 mL of drain fluid was inoculated into thioglycollate broth. The aerobic agar plates were incubated at 35°C in 5% to 7% CO2 for 4 days, or until positive. The anaerobic agar plate was incubated anaerobically for 7 days, or until positive. The thioglycollate broth was incubated anaerobically for 14 days, or until positive. Growth was reported as negative, growth from broth only, or if there was growth on a plate, it was quantitated as 1+, 2+, 3+, or 4+ according to standardized laboratory protocol. All isolates were speciated.
For drain tubing culture, the tube was rolled over the surface of a sheep blood agar plate 4 times in different directions, and the plate incubated aerobically at 35°C in 5% to 7% CO2 for 4 days, or until positive. Growth was identified and reported semiquantitatively as less than 10 colony-forming units (CFUs), 10 to 19 CFUs, 20 to 50 CFUs, 51 to 100 CFUs or greater than 100 CFUs. Laboratory personnel were blinded to patients' drain care regimens, and results of study cultures were not reported or included in the participants' medical records.
The primary endpoint of the study was bacterial growth in the fluid of the drainage bulb at the 1-week follow-up visit. Estimating a bacterial colonization rate of 33% in drainage fluid at 1 week, a sample size of 100 was projected to provide 80% power to detect a 70% reduction in colonization with antisepsis measures. A drain fluid culture with bacterial growth of 1+ or greater was defined as positive on the basis of the assumption that growth from broth only should not be clinically meaningful. A positive drain tubing culture was defined as growth of greater than 50 CFU on the basis of prior published data demonstrating catheter site inflammation in a majority of subjects with greater than 50 CFU. Given the limitations in selecting these cutoffs, we examined endpoints not dependent on the chosen cutoff for positivity; the ordinal quantification of degree of colonization was also analyzed for both drain fluid and drain tubing cultures. In samples colonized with multiple organisms, the highest degree of quantification across all organisms was used to classify the sample for analysis. SSIs included any of the following within 30 days after operation: purulent drainage, positive aseptically collected culture from the wound, signs of inflammation with opening of incision and absence of a negative culture, or physician diagnosis of infection (which could include cellulitis). Cases of equivocal SSI were reviewed in detail by the research team without knowledge of the assigned treatment arm and were decided by consensus.
Two sample comparisons at the per patient level were performed using 2-sample t tests or Wilcoxon rank sum tests for continuous and ordinal variables and likelihood ratio [chi] tests for nominal variables. Drain duration and volume were compared using linear mixed effects models to account for multiple drains within patient. Colonization rates were analyzed on a per drain level with generalized linear mixed models (random intercept logistic regression) to account for the nonindependence of multiple drains from the same patient. Ordinal colonization quantification levels were compared between treatment arms using a generalized estimating equations approach to fit ordinal logistic regression. A per patient analysis of drain colonization was also performed, as was a comparison of SSI rates, using [chi] tests. The sign test for paired proportions was used to compare positivity rates between mastectomy and axillary drains in patients who had both.P values of <0.05 were considered statistically significant. Analysis was performed using SAS (Version 9.2; SAS Institute Inc, Cary, NC).
Methods
Study Population
After approval by the Mayo Clinic Institutional Review Board, eligible subjects were recruited prospectively from the breast surgical practice at Mayo Clinic in Rochester, MN, between January 2009 and May 2011. Individuals were included if undergoing total mastectomy and/or axillary lymph node dissection for benign or malignant disease in which surgical drains were placed. Subjects were ineligible if they were pregnant, had received antibiotics within 14 days before surgery, had a known allergy to chlorhexidine, or were undergoing immediate reconstruction (because of the common use of postoperative antibiotics in this subgroup).
Randomization
After informed consent, subjects were randomized to either the standard drain care regimen or the drain antisepsis regimen by a computerized randomization program, using dynamic allocation and stratifying by surgical procedure (mastectomy or lumpectomy with axillary dissection), surgeon, and body mass index (BMI <30 or >=30). In the event of bilateral procedures, patients with a unilateral cancer had sample collection and analysis from the side affected with cancer. Subjects who had bilateral cancer or bilateral prophylactic mastectomies underwent computerized randomization to select the side to be evaluated on study. The operating surgeon remained blinded to the assigned treatment arm.
Perioperative Standardization
All subjects received a single dose of intravenous preoperative cefazolin (dosed per weight) within 30 minutes before skin incision. In the case of cefazolin allergy, vancomycin or levofloxacin was alternate, and antibiotics were redosed intraoperatively when appropriate. A chlorhexidine/alcohol skin prep (ChloraPrep; CareFusion Corporation, San Diego, CA) or iodine/alcohol (DuraPrep; 3M, St Paul, MN) was used per surgeon preference. The surgical drainage tube used was a 15Fr round channel hubless drain secured with nonabsorbable monofilament suture. Antibiotics were not permitted beyond 24 hours after surgery. Patients could shower 48 hours after surgery, but immersion bathing was not permitted.
Drain Care Regimens
Study subjects and family members received personal instruction on drain care on the first postoperative day (POD) by the nurse study coordinator, and they were advised not to divulge the drain care regimen to their surgeon. All subjects in both treatment arms were instructed to strip the drain tubing, empty the bulb, and record fluid volume at least twice daily. Individuals assigned to standard drain care were also advised to cleanse the drain exit site with prepackaged 70% isopropyl alcohol wipes twice daily and to cover the drain site with a sterile gauze dressing. Subjects in the drain antisepsis arm were shown how to cleanse the drain exit site with alcohol and then apply a chlorhexidine gluconate disc dressing (Biopatch®; Johnson & Johnson Medical) at the drain site and secure it with an adherent sterile transparent occlusive dressing (Fig. 1). The chlorhexidine disc and occlusive dressing were changed every 3 days until drain removal. In addition, subjects in the drain antisepsis arm were instructed to perform antiseptic irrigation of the drainage bulb twice daily as follows: instill 10 mL of dilute Dakin's solution (0.0125% buffered sodium hypochlorite) into the drainage bulb via the exit valve (prepped with alcohol), swish occasionally over 10 minutes, and then empty and return the bulb to suction. At the time of showering, the chlorhexidine disc/occlusive dressing was left intact.
(Enlarge Image)
Figure 1.
Chlorhexidine disc dressing with occlusive adherent dressing.
Management of Multiple Drains
If more than 1 drain was placed per surgical site (ie, 2 drains in the setting of a modified radical mastectomy), then both drains associated with that surgical site were treated according to the assigned treatment arm. Each drain associated with the surgical site was evaluated separately for bacterial colonization endpoints.
Follow-up Visits and Cultures
For 30 days after operation, a standardized data collection form was completed at every follow-up visit, with details including drainage volume, erythema, or skin changes at the incision and drain sites, and evidence of seroma or infection. In addition, the medical record was reviewed to screen for late infections. Blinding of the surgeon was maintained at postoperative visits by the study coordinator removing all dressing materials before surgeon evaluation. A mandatory follow-up visit occurred at 1 week (on POD 7 ± 1 day) for study cultures and for clinical evaluation for signs of infection or adverse reactions to drain antisepsis regimen. If drains were ready for removal before this, all cultures were obtained on the day of drain removal. At each visit, compliance with the antiseptic interventions was assessed by the study coordinator, who asked the subjects whether they had any difficulties that prevented completing the prescribed regimen. For patients with clinical evidence of infection, diagnostic cultures and antibiotic therapy were performed per routine clinical care. Guidelines for drain removal specified output of 30 mL or less per 24 hours for 2 consecutive days or at POD 19, whichever came first. If drain removal did not occur at the 1-week visit, then a repeat culture of drain fluid was obtained on the day of drain removal; therefore, some subjects had drain fluid cultures at 2 time points. Drain tubing cultures at removal were added to the protocol after the study was underway and are available in 76 of 100 patients.
Microbiology
At the 1-week visit, a 2-mL sample of drain fluid from the bulb was obtained aseptically for semiquantitative aerobic and anaerobic cultures. On the day of drain removal, cultures were obtained of both drain bulb fluid and drain tubing. Drains were removed in a sterile fashion after chlorhexidine preparation and sterile draping of the drain exit site. A 5-cm portion of the subcutaneous drain tubing was harvested, starting approximately 1 to 2 cm internal to the skin exit site.
For drain fluid culture, 1 to 2 drops of fluid were inoculated onto sheep blood, eosin methylene blue, and colistin-nalidixic acid agar plates, and anaerobic sheep blood agar plates, and 1 mL of drain fluid was inoculated into thioglycollate broth. The aerobic agar plates were incubated at 35°C in 5% to 7% CO2 for 4 days, or until positive. The anaerobic agar plate was incubated anaerobically for 7 days, or until positive. The thioglycollate broth was incubated anaerobically for 14 days, or until positive. Growth was reported as negative, growth from broth only, or if there was growth on a plate, it was quantitated as 1+, 2+, 3+, or 4+ according to standardized laboratory protocol. All isolates were speciated.
For drain tubing culture, the tube was rolled over the surface of a sheep blood agar plate 4 times in different directions, and the plate incubated aerobically at 35°C in 5% to 7% CO2 for 4 days, or until positive. Growth was identified and reported semiquantitatively as less than 10 colony-forming units (CFUs), 10 to 19 CFUs, 20 to 50 CFUs, 51 to 100 CFUs or greater than 100 CFUs. Laboratory personnel were blinded to patients' drain care regimens, and results of study cultures were not reported or included in the participants' medical records.
Endpoints and Statistical Power
The primary endpoint of the study was bacterial growth in the fluid of the drainage bulb at the 1-week follow-up visit. Estimating a bacterial colonization rate of 33% in drainage fluid at 1 week, a sample size of 100 was projected to provide 80% power to detect a 70% reduction in colonization with antisepsis measures. A drain fluid culture with bacterial growth of 1+ or greater was defined as positive on the basis of the assumption that growth from broth only should not be clinically meaningful. A positive drain tubing culture was defined as growth of greater than 50 CFU on the basis of prior published data demonstrating catheter site inflammation in a majority of subjects with greater than 50 CFU. Given the limitations in selecting these cutoffs, we examined endpoints not dependent on the chosen cutoff for positivity; the ordinal quantification of degree of colonization was also analyzed for both drain fluid and drain tubing cultures. In samples colonized with multiple organisms, the highest degree of quantification across all organisms was used to classify the sample for analysis. SSIs included any of the following within 30 days after operation: purulent drainage, positive aseptically collected culture from the wound, signs of inflammation with opening of incision and absence of a negative culture, or physician diagnosis of infection (which could include cellulitis). Cases of equivocal SSI were reviewed in detail by the research team without knowledge of the assigned treatment arm and were decided by consensus.
Statistical Analysis
Two sample comparisons at the per patient level were performed using 2-sample t tests or Wilcoxon rank sum tests for continuous and ordinal variables and likelihood ratio [chi] tests for nominal variables. Drain duration and volume were compared using linear mixed effects models to account for multiple drains within patient. Colonization rates were analyzed on a per drain level with generalized linear mixed models (random intercept logistic regression) to account for the nonindependence of multiple drains from the same patient. Ordinal colonization quantification levels were compared between treatment arms using a generalized estimating equations approach to fit ordinal logistic regression. A per patient analysis of drain colonization was also performed, as was a comparison of SSI rates, using [chi] tests. The sign test for paired proportions was used to compare positivity rates between mastectomy and axillary drains in patients who had both.P values of <0.05 were considered statistically significant. Analysis was performed using SAS (Version 9.2; SAS Institute Inc, Cary, NC).