- Department of Neurology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
- Department of Neurosurgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
- Department of Radiology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
- Department of Neurology University of Sao Paulo, Sao Paulo, Brazil.
- Department of Neurosurgery, University of Sao Paulo, Sao Paulo, Brazil.
Iuri Santana Neville, MD, PhD, Neurosurgery Service, Instituto do Cancer do Estado de Sao Paulo, Av Dr. Arnaldo 251 Cerqueira Cesar, CEP: 01246-000, Sao Paulo, Brazil.
DOI:10.25259/SNI_423_2022Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Joao Paulo Mota Telles1, Vitor Nagai Yamaki2, Ricardo Andrade Caracante3, Victor Hugo Barboza Martins2, Wellingson Silva Paiva4, Manoel Jacobsen Teixeira5, Eberval Gadelha Figueiredo5, Iuri Santana Neville2. Early versus delayed debridement for surgical site infection after oncological neurosurgery. 01-Jul-2022;13:283
How to cite this URL: Joao Paulo Mota Telles1, Vitor Nagai Yamaki2, Ricardo Andrade Caracante3, Victor Hugo Barboza Martins2, Wellingson Silva Paiva4, Manoel Jacobsen Teixeira5, Eberval Gadelha Figueiredo5, Iuri Santana Neville2. Early versus delayed debridement for surgical site infection after oncological neurosurgery. 01-Jul-2022;13:283. Available from: https://surgicalneurologyint.com/?post_type=surgicalint_articles&p=11688
Background: There are no guidelines on the management of surgical site infection (SSI) in neurosurgery. This study sought to analyze whether early debridement improved survival compared to antibiotic therapy alone in patients with postcraniotomy infections after oncological neurosurgeries.
Methods: We retrospectively reviewed patient records from 2011 to 2019 to identify patients that had been reoperated for the debridement of SSI after brain tumor resection. If SSI was suspected but not clinically evident, the diagnosis was confirmed by cerebrospinal fluid (CSF) analysis or contrast-based imaging examinations. Immediately after diagnosis, broad-spectrum antibiotics were started for all patients.
Results: Out of 81 SSI cases, 57 underwent debridement. Two patients were reoperated 3 times, and three had two surgeries, resulting in a total of 64 procedures. The number of days between SSI diagnosis and surgical intervention did not influence mortality in both univariate and multivariable analyses (Hazard ratio [HR] 1.03, 95% CI 0.93–1.13). Early debridement (P = 0.53) or hospital length of stay (LOS) (P = 0.16). Higher neutrophil-lymphocyte ratios (NLRs) were associated with the lower survival (HR 1.05, 95% Confidence interval [CI] 1.01–1.08). Multiple cutoffs were tested and values above 3.5 are more significantly associated with worse outcomes (HR 2.2; 95%CI 1.1–4.2).
Conclusion: Early debridement does not seem to influence the survival, rates of antibiotic at discharge, or hospital LOS of patients presenting with SSI after neurosurgery for intracranial tumors. High NLRs are strong predictors of worse prognosis in this population.
Keywords: Antibacterial agents, Brain neoplasms, Debridement, Surgical wound infections, Survival analysis
Patients submitted to any operation are susceptible to surgical site infections (SSIs), defined as an infectious process arising until 30 days after the procedure without prosthetic material or 1 year if prosthetic material is implanted.[
Patients with brain tumors usually present one or more risk factors for postcraniotomy infection, namely, prolonged operative times, reoperations, sinus contamination, cerebrospinal fluid (CSF) leak, and radiation therapy.[
There is no concise guideline on the management of SSI in neurosurgery.[
MATERIALS AND METHODS
We retrospectively reviewed patient records from 2011 to 2019 to identify patients that had been reoperated for the debridement of SSI after brain tumor resection. Out of 81 SSI cases, 57 had undergone debridement. Patient data retrieved included age, gender, hospital length of stay (LOS), necessity of antibiotics at discharge, primary tumor site, and presence of metastasis (both intra and extracranial).
If SSI was suspected but not clinically evident, the diagnosis was confirmed by CSF analysis or contrast-based imaging examinations, such as head computed tomography or magnetic resonance imaging. Immediately after diagnosis, broad-spectrum antibiotics were started for all patients. Debridement consisted of wound exposure, collected samples for microbiological analysis, thorough irrigation with saline, removal of any devitalized tissue, with or without CSF leak repair, and removal of infected bones. It was indicated in case of persistent inflammatory signs on surgical site, worsening in laboratory work-up, persistent fever, or CSF leak. The interval between SSI diagnosis and surgical debridement was also recorded. All patients had undergone antibiotic prophylaxis with first generation cephalosporins in their previous surgeries.
Clinical and laboratory baseline data were collected from the 1st day of SSI diagnosis. CSF cultures were analyzed to diagnose meningitis and imaging was analyzed to diagnose abscesses. Functional assessment was recorded according to the World Federation of Neurological Societies (WFNS) scale before and after surgery, and patients who were not deceased had their follow-up censored at their last outpatient appointment.
Leukocyte differential and neutrophil-lymphocyte ratio (NLR) were studied as possible predictors of survival. Due to the diversity of primary tumor sites (including hematologic neoplasia), the differentials were included as percentages. Primary central nervous system (CNS) tumors included glioblastoma multiforme, astrocytoma, and oligodendroglioma. Non-CNS tumors (metastases) included melanoma, non-small cell lung cancer, and clear cell carcinomas.
Data are presented as mean (standard deviation) for normally distributed variables, median (interquartile range, IQR) for other continuous variables, and frequencies (valid %) for categorical variables. Welch’s, Wilcoxon’s, and Chi-squared tests were used for comparison of means and frequencies, as appropriate based on the variable’s nature. Survival was studied using Kaplan–Meier survival curves and Cox proportional hazards regressions. Age and metastatic diseases (vs. primary CNS tumor) were included in the multivariable models due to biological plausibility, because both were considered to influence overall survival.
Linearity and proportional hazards assumptions were verified both numerically graphically through Schoenfeld and Martingale residuals. Values of P < 0.05 were considered significant. Statistical analyses were performed using R (R Foundation for Statistical Computing. Vienna, Austria, 2018).
Over this period, 57 patients were operated for the debridement of SSI. Mean patient age was 52.0 (±13.7) years and 18 (31.6%) were female. Concerning the primary tumor site, 33 (57.9%) had CNS neoplasms, 19 (33.3%) had nonCNS solid neoplasms, 2 (3.5%) had hematologic neoplasms, and three metastatic carcinomas of unknown primary site (5.3%). All patients had either primary CNS tumors or metastatic lesions. Median preoperative WFNS score was 2 (IQR 2). Three patients (5.3%) had associated meningitis and 8 (14%) had intradural abscesses [
Seven of the primary surgeries were in the posterior fossa (12.3%). Five patients underwent multiple debridements: two patients were operated three times and three had two debridements, resulting in a total of 64 procedures. The most commonly identified bacteria were methicillin-sensitive Staphylococcus aureus (MSSA), in 16 (28.1%) cases, followed by MSSA, in 15 (26.3%). In ten cases, culture reports were negative [
Time between SSI diagnosis and debridement ranged from 0 to 17 days, but the median was 2 days (IQR 4.75). At discharge, the median WFNS score was 1 (IQR 2). Patients’ median follow-up time was 326.5 days. During follow-up, 38 (66.6%) patients died. The median follow-up of these patients was 276 days (IQR 585.75) and five of them (8.8%) survived <30 days.
Time between infection diagnosis and debridement was first analyzed as a continuous variable [
Kaplan–Meier curves for different time periods between infection diagnosis and debridement. Surgical debridement occurred at various different time periods from clinical diagnosis of surgical site infection (SSI). The curves represent cumulative survival for patients who underwent debridement <24 h after SSI diagnosis (full line), >24 h (dashed line), >48 h (dotted line), and >72 h (dash-and-dot line). Vertical dashes represent censored data. There were no significant differences in survival among groups (log-rank, all P > 0.05).
Antibiotics were maintained at discharge for 25 patients (46.3%) and early (<24 h) debridement did not influence this rate (χ2 = 0.40, P = 0.53). The same was true for different time frames (48 h and 72 h, both P > 0.4). Median LOS was 21 days (IQR = 23.5) in general, 15 days (IQR = 14) for those who underwent debridement <24 h, 26 days (IQR = 30) for those who underwent debridement > 24 h, and 23.5 days (IQR = 20.75) for debridement >48 h. No differences were observed for any of the time frames: 24 h (P = 0.16) and 48 h (P = 0.98).
Hematologic parameters, NLR, and prognosis
Hematologic parameters were tested to identify potential outcome predictors of SSI after craniotomy for brain tumor resection. Among the differential leukocyte count, lower survival was observed in patients with a higher percentage of neutrophils (univariate, HR 1.03, 95% CI 1.003–1.05), whereas the opposite was true regarding lymphocytes (univariate, HR 0.95, 95% CI 0.92–0.97). Percentages of eosinophils, basophils, and monocytes did not influence survival.
Higher NLR predicted worse prognosis in the multivariable analyses, adjusted for age, and metastatic disease [
Significance of different NLR thresholds. Significance of multiple neutrophil-lymphocyte ratios (NLR) in multivariable models adjusted for age and presence of metastasis (compared to primary CNS tumors). NLR becomes a robust predictor of worse prognosis for values > 3.5, although the NLR > 4.0 slightly missed the established significance threshold (P = 0.058).
Our results demonstrate that early debridement does not seem to influence mortality for patients with SSI after craniotomies for brain tumor resection. There were also no differences regarding LOS at the hospital or necessity of antibiotics at discharge. The NLR is a robust prognostic marker in this population.
Multiple factors inherent to patients with cancer can predispose them to infections and potentially impair their ability to handle pathogens. These factors might be patient-related (advanced age, comorbidities, and functionality), disease-related (metastasis or bone marrow involvement), or treatment-related conditions (chemotherapy regimen and dosage).[
While risk factors and prophylaxis are better studied and standardized,[
Because surgical debridement was taken at many different timings, we analyzed this time-interval under two different perspectives to answer the same question: is it safe to start clinical treatment as first-option treatment for SSI?
The continuous analysis [
Even though the majority of patients underwent to debridement surgery, we believe that initial antibiotic course has several advantages for these patients. The early systemic inflammatory response is diminished; therefore, patients are often operated on better clinical conditions. Antibiotics trial can also attenuate a significant portion of SSI leading to less invasive surgical procedures. Our records demonstrated that almost 30% were managed with clinical treatment avoiding unnecessary surgical risks.
Inflammation and prognosis
Inflammation plays a critical role in both oncological and infectious diseases.[
Our results have demonstrated that high NLR at the 1st day of SSI diagnosis is a strong predictor of worse prognosis for patients with SSI after surgeries for intracranial tumors. Bao et al.[
Strengths and limitations
Our paper has limitations. The sample size is relatively small, with 57 patients and 64 procedures, and patients can be heterogeneous within the wide clinical spectrum of SSI. Other important outcome measures need additional assessment, such as morbidity, time until infection resolution, or cost analyses. Furthermore, the retrospective design also brings potential biases, such as incomplete records and possible unknown confounders. Indeed, this matter should ideally be tested on a randomized trial to draw definitive conclusions.
However, a study of over 2600 craniotomies for tumors resulted in only 39 debridement’s.[
Early debridement does not seem to influence the survival, rates of antibiotic at discharge, or hospital LOS of patients presenting with SSI after neurosurgery for intracranial tumors. In this setting, delayed debridement based on sound clinical judgment can be considered safe. High NLRs are strong predictors of worse prognosis in this population.
For this type of study, formal consent is not required.
Declaration of patient consent
Patients’ consent not required as patients’ identities were not disclosed or compromised.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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