Abstract
Abstract
Background:
To date, without placement of a drain, seroma formation cannot be avoided after axillary lymph node dissection (ALND). The purpose of this study was to evaluate the effect on drainage volume of pre-closure axillary lavage with physiologic saline, gentamicin solution, or clindamycin solution.
Methods:
A randomized study was performed between January 2013 and October 2014. Inclusion criteria were a diagnosis of breast neoplasm and plans to undergo an elective ALND because of axillary metastases. The patients were randomized into three groups: Two lavages with 500 mL of physiologic saline (Group 1), lavage with 500 mL of saline followed by lavage with 500 mL of a 240-mg gentamicin solution (Group 2), and lavage with 500 mL of saline followed by lavage with 500 mL of a 600-mg clindamycin solution (Group 3).
Results:
A total of 51 patients were included. The mean number of days with a drain in place was 7.1±3 in Group 1, 4.1±1.2 in Group 2, and 6.4±2.1 in Group 3 (p<0.001). Total drainage volume before tube removal was 435.3±220.1 mL in Group 1, 155.2±82.4 mL in Group 2, and 352.3±212.9 mL in Group 3 (p=0.03). In a pairwise analysis, irrigation with gentamicin solution achieved a lower drainage volume and a reduction in the number of days of drainage maintenance compared with the other two groups.
Conclusion:
The post-operative output of the axillary drain is substantially lower in patients undergoing lavage of the surgical bed with a gentamicin solution than in patients undergoing lavage with physiologic saline or clindamycin solution.
A
Gentamicin presents an excellent spectrum of activity against saprophytic pathogens such as Staphylococcus epidermidis, which frequently is involved in axillary surgical site infections (SSIs) [10]. A previous study by our group showed that the irrigation of the axillary bed with gentamicin solution decreased drainage as a result of a reduction in bacterial contamination [11].
Clindamycin has demonstrated a wide spectrum of activity against gram-positive and anaerobic flora. It has been used widely against infections caused by saprophytic skin flora that in certain circumstances may cause infection [12]. Given that clindamycin shows a wider spectrum than gentamicin against saprophytic skin flora, a greater reduction in the drainage volume after ALND can be expected. The purpose of this study was to evaluate the effect of axillary lavage with a clindamycin solution, a gentamicin solution, or physiologic saline before incision closure on the drainage volume and day of drainage tube removal.
Patients and Methods
Patients
A randomized study was performed in the Breast Unit of the General University Hospital of Elche between January 2013 and October 2014. The sample size was calculated on an expected drainage volume of 169 mL in the group undergoing lavage with antibiotic solution and 465 mL in the control group based on our epidemiologic data [11]. At 80% power and a significance of p<0.050, it was calculated that 17 patients were required in each arm of the study.
Inclusion criteria were a diagnosis of breast neoplasms and plans to undergo an elective ALND of Berg's levels I and II because of axillary metastases determined pre-operatively by core biopsy or evidence of metastasis in the SLNB in the intra-operative or differential analysis. Exclusion criteria were allergy to any of the antibiotic drugs to be used, chronic renal failure secondary to possible toxicity of gentamicin, and planned modified radical mastectomy.
The patients were randomized by means of an Internet module into three groups. All patients underwent a first lavage of the axillary surgical bed with physiologic saline. Group 1 underwent a second lavage with saline. Group 2 had a second lavage with a 240-mg gentamicin solution (Group 2), and Group 3 had a second lavage with a 600-mg clindamycin solution. Pre-operative systemic antibiotics (amoxicillin–clavulanic acid 2 g intravenously [IV]; a single dose within 30 min of incision) were employed in all groups. The patients were blinded as to whether they received saline, gentamicin, or clindamycin. Surgical dissection was performed using a Harmonic Scalpel (Ultracision; Ethicon Endosurgery, Johnson and Johnson, Cincinnati, OH, USA). Once the ALND was finished, a Redon drain was placed and connected to a low-pressure vacuum device.
Irrigation technique
The lavages were performed immediately prior to closure of the incision after the drain had been placed in the surgical cavity. After the second lavage, the subcutaneous tissue was closed with simple sutures of polyglactin 3-0 and the skin with an intradermic suture of polyglitone 3-0. Finally, a bandage was placed in the axilla.
Indication for drain removal
After discharge, the patient was asked to quantify the drainage volume daily. The drain was removed when the volume was <30 mL/d. The patients were examined two weeks after surgery to ensure the absence of a seroma, revealing that the drain had not been removed prematurely in any patient.
Variables
The clinical variables recorded were age, co-morbidities, complications (incision infection, seroma), death, hospital stay, daily drainage volume, and day of drain removal. The histologic variables were the number of lymph nodes isolated and the number containing metastases, tumor size, and tumor stage.
Statistics
Statistical analysis was performed with SPSS version 19.0 for Windows. Quantitative variables that followed a normal distribution were defined by the mean and standard deviation. For non-Gaussian variables, the median and range were used. Qualitative variables were defined by the number and percentage of cases. Comparison of variables was performed with the Student t-test, analysis of variance (ANOVA), and the Pearson correlation method for quantitative variables following a Gaussian distribution. Non-parametric tests (Mann-Whitney, Kruskal-Wallis, and Spearman correlation) were used for non-Gaussian variables. Comparison of qualitative variables was performed with the χ2 test; in those cases with fewer than five observations in the cell, the Fisher exact probability method was used. In all analyses, p<0.05 was regarded as significant.
The study protocol and the manuscript were approved by the local ethics committee, and all the patients granted informed consent for the surgical intervention and inclusion in the clinical trial.
Results
A total of 51 patients were included in the study, all of them female, with a mean age of 55.6±13.3 years. There were no significant differences in age, co-morbidities, time of performing ALND, number of isolated and metastatic lymph nodes, primary tumor size, or tumor stage among the groups (Table 1).
SD=standard deviation.
There were no complications (seroma or incisional SSI) or deaths in any of the groups. The median hospital stay was 3 d (range 1–3 d) in all the groups. The mean number of days with the drain in place was 7.1±3 in Group 1, 4.1±1.2 in Group 2, and 6.4±2.1 in Group 3 (p<0.001). The total drainage volume was 435.3±220.1 mL in Group 1, 155.2±82.4 mL in Group 2, and 352.3±212.9 mL in Group 3 (p=0.03). The clinical data are summarized in Table 2.
SD=standard deviation.
In a pairwise analysis of the time of drainage maintenance, comparing Group 1 with Group 2, a mean difference of 3 d (95% confidence interval [CI] 1.6–6.8 d; p<0.001) was observed. A mean difference of 280.1 mL (95% CI 135–498 mL; p=0.004) was observed. Comparing Group 1 with Group 3, there were no significant differences in the days of drain maintenance or the volume of discharge. Comparing Group 2 with Group 3, a mean difference of 2.3 d (95% CI 1.1–3.4 d; p=not significant) was observed. Referring to the mean total drainage volume, a mean difference of 187.1 mL (95% CI 73–292 mL; p=0.01) was observed.
Discussion
Although ALND is considered a clean operation, it presents a greater SSI rate than those associated with other clean procedures [13]. Some authors have proposed that the axillary and breast folds are dirty body locations, where the sweat can accumulate, justifying the finding of greater infection rates. Moreover, this is one of the main reasons to support the administration of systemic antibiotic prophylaxis, as breast and axillary surgery might be linked to incisional SSI rates as high as 15%, rates associated with clean contaminated rather than clean operations [14]. In our previous study, we observed that there is bacterial contamination in as many as 60% of patient, and this high contamination rate may predispose to the development of SSI. The microorganisms isolated in the surgical bed at ALND were S. epidermidis and anaerobic saprophytic flora of the skin [11]. On the basis of these previous results of our group, we decided to expand the benefit analysis of topical antibiotic prophylaxis to clindamycin, as theoretically, clindamycin has a wider spectrum of activity against Staphylococcus spp. and anaerobic flora.
The main causes of lymphorrhea are the gaps resulting from the section of the lymphatic capillaries. Moreover, the surgical dissection is an aggression that starts an inflammatory response, and bacterial contamination increases and prolongs it. This action probably increases the lymphatic flow and delays the repair of the capillary gaps. As we have already demonstrated, the use of local intra-operative antibiotics during surgery can decrease the post-operative degree of lymphorrhea; the irrigation of the axillary bed with a gentamicin solution achieved a reduction in the drainage volume [11]. Gentamicin presents a broad spectrum against Staphylococcus spp. but no efficacy against anaerobic microorganisms. Considering that anaerobic flora can be involved in contamination of the surgical bed, we hypothesized that irrigation with clindamycin would show even better results than treatment with gentamicin. Nevertheless, we observed that lavage with clindamycin solution produced worse results, as judged by drainage volume and days until drain removal, than gentamicin irrigation, not substantially different from the results of saline irrigation.
Probably the superiority of gentamicin resides in the recent evolution of resistance of microorganisms to clindamycin. Recent studies have shown that the resistance rate of Staphylococcus spp. to clindamycin tops 40% [15,16]. As previously mentioned, most axillary infections are caused by Staphylococcus spp. The fact that the resistance rate of the organism to the antibiotic is so high means frequent failure to eradicate this microorganism, which probably is involved in the contamination and inflammatory response in the axillary bed. Thus, the volume of discharge remains as high as after irrigation with physiologic saline.
One of the main limitations of this study is the lack of analysis of microorganisms present in the surgical bed after every lavage. Probably this would have reinforced the hypothesis of a high rate of resistance to clindamycin. Probably, when using broad-spectrum antibiotics, a decrease in the drainage volume could be obtained. However, careful selection of antimicrobial drugs is necessary, as their wide use can lead to the development of resistance by nosocomial strains.
Conclusion
The post-operative volume of axillary drainage is substantially lower in patients undergoing lavage of the surgical bed with a gentamicin solution than in patients undergoing lavage with physiologic saline or clindamycin solution. This trial is listed in ClinicalTrials.gov with identifier NCT02314806.
Footnotes
Author Disclosure Statement
No competing financial interests exist.