The risk factors of surgical site infection following posterior cervical spine surgery

Background: Surgical site infection (SSI) is a common complication following posterior cervical spine surgery, imposing a high burden on patients and society. However, information about its characteristics and related risk factors is limited. We designed this study intended to address this issue. Methods: From January 2011 through October 2020, a total of 405 patients diagnosed of cervical degenerative diseases (cervical spondylotic myelopathy, ossication of posterior longitudinal ligament and cervical disk herniation) who were treated with unilateral open-door lamnioplasty surgeries were enrolled in this study. We divided the patients into the SSI group and the non-SSI group and compared their patient-specic and procedure-specic factors. Univariate and multiple logistic regression analyses were performed to determine risk factors. Results: There were signicant differences between groups in subcutaneous fat thickness (FT) (P<0.001), ratio of subcutaneous FT to muscle thickness (MT) (P<0.001), preoperative Japanese Orthopaedic Association (cid:0) JOA (cid:0) Scores (P< 0.003), preoperative serum albumin (P< 0.001), postoperative drainage (P<0.004), time of draining (P<0.001). Logistic regression analysis of these differences showed that ratio of subcutaneous FT/MT, preoperative JOA score, preoperative serum albumin and longer time of draining were signicantly related to SSI (P<0.05). Conclusion: Ratio of subcutaneous FT/MT, preoperative JOA score, preoperative serum albumin and longer time of draining are identied as the independent risk factors of SSI in posterior cervical spine surgeries. Identication of these risk factors could be useful in reducing SSI incidence and patients counseling.


Introduction
Surgical site infection (SSI) the most common complication after spinal surgery is an infection of the tissues, organs, or spaces exposed by surgeons during the performance of an invasive procedure [1][2][3] . SSI was classi ed as super cial, deep, or organ space. Compared with lumbar surgeries, cervical surgeries cases were associated with a signi cantly lower rate of infection 4 . Meanwhile, posterior cervical spine surgeries cases having a signi cantly higher rate of infection than anterior cervical surgeries cases with consequences ranging from super cial to deep infection 5 . The incidence of postoperative surgical site infections (SSIs) after posterior cervical spine surgeries is reported to range from 1.4-13% 6,7 . SSI leads to devastating outcomes including requires multiple readmissions, wound debridement or implant removal and increasing mortality, which results in readmission to the hospital, poor outcomes and additional hospitalization expenses causing patients' physical, mental, and economic burdens [8][9][10] .
Although advances have been made in infection control practices, the incidence of SSI after posterior cervical surgery ranges from 1.3-14%, Several risk factors for SSI in posterior cervical spine surgeries are increasingly being investigated. Many estimated risk factors have been reported in previous studies, such as advanced age, higher body mass index (BMI > 30 kg/m 2 ), smoking, diabetes, malnutrition (preoperative albumin level < 3.5 g/dL), history of infection in the surgical site, preoperative steroid therapy, blood loss, implant, and prolonged operative time (> 3 hours) [11][12][13][14][15][16] . Meanwhile, bacterial culture indicated that the most common causative microorganisms of SSI in spinal surgery are Staphylococcus aureus and other members of Staphylococcus species 17,18 . However, the results in these previous studies were not always consistent and there were few studies about the risk factors of SSI following posterior cervical spine surgeries. In this study, we investigated the frequency of SSI and evaluated the risk factors for SSI in a Chinese population by comparing patient-related and procedure-related factors to identify cases of SSI and determine the factors that modify the risk of SSI to relief the burden on society.

Patient Population
This was a retrospective clinical study. From January 2011 to October 2020, 435 patients following posterior cervical spine surgeries at First A liated Hospital of Dalian Medical University and were included in this study and were observed for a minimum of 2 months postoperatively. 30 patients in this experiment were lost to follow-up among them. Information gathered included demographic details, cause of disorder, diagnosis, radiologic ndings, and laboratory investigations. Preoperative, intraoperative, and postoperative ndings were recorded. All patients aged 18 years or older who had cervical degenerative diseases (cervical spondylotic myelopathy, ossi cation of posterior longitudinal ligament and cervical disk herniation) treated by unilateral open-door lamnioplasty surgeries were included. The exclusion criteria were as follows: age < 18 years, traumatic fractures, and pathologic fractures (metastasis, tuberculosis) and 405 patients were enrolled. All surgical procedures were performed in operating rooms equipped with vertical laminar air ow. All surgical personnel wore body exhaust suits. We administered antibiotic prophylaxis just before surgery and 72 hours postoperatively for all patients. Each patient in the study underwent classic open-door lamnioplasty surgeries. A deep one-off negative pressure drain was inserted, and the fascia was closed meticulously, followed by closure of the wound. The drain was removed about 2 days postoperatively when the discharge was observed to be < 50 ml. The postoperative rehabilitation protocols were similar in all patients. Identi cation of SSI The diagnosis of SSI involves the interpretation of combined clinical, laboratory, and occasionally radiologic ndings. SSI is considered as a diagnosis within 30 days of surgery in the absence of implants, and up to 1 year postoperatively in the presence of surgical implants. In this study, the de nition of SSI was based on the Centers for Disease Control and Prevention de nition. Super cial infection involves the skin and subcutaneous tissue only, occurring within 30 days after the operation, leading to pain, tenderness, redness, and heat over the site. Deep infection involves the fascia and muscle, occurring within 30 days after the operation (if no implant was left in place) or within 1 year (if the implant was left in place), often resulting in fever (> 38℃), pain, tenderness, and abscess formation. Organ infection includes septic discitis, vertebral osteomyelitis, and epidural abscess, leading to possible purulent drainage and abscess formation 1 . The microbiological culture results from all patients who experienced SSI were collected and recorded. In patients who underwent open debridement, microbiological cultures were taken to con rm the presence of SSI and to decide further treatment.

Data collection and outcome evaluations
The patients were divided into an SSI group and a non-SSI group in this study. We compared their patientrelated factors such as: age, gender, BMI, muscle thickness(MT), subcutaneous fat thickness(FT), diabetes mellitus(DM), hypertension, ischemic heart disease, steroid use, rheumatoid arthritis, preoperative Japanese Orthopaedic Association(JOA)Scores, previous SSI, other infections such as pulmonary infection, urinary infection, and so on during the perioperative period, preoperative American Society of Anesthesiologists score, preoperative Visual Analogue Scale, preoperative temperature, preoperative white blood cell count, preoperative hematocrit, preoperative and postoperative hemoglobin, preoperative total lymphocyte count, preoperative serum albumin) and procedure-related factors (operative time, operated levels, estimated blood loss, postoperative drainage, time of draining, allogeneic blood transfusion, intraoperative rapid sterilizer use, local intrawound vancomycin antibiotic powder, dural tear, perioperative invasive vascular catheterization, postoperative prophylactic antibiotics).

Statistical Analysis
The mean and standard deviation were calculated for continuous variables; number and percentage were calculated for categorical variables. Firstly, a univariate logistic regression analysis was performed to evaluate the relationship between each categorical variable and SSI. The t-test or Mann-Whitney U test was used for continuous variables, depending on the data distribution (equal variance and normality or not). A P value < 0.05 was considered to be signi cant. Further, all the related variables were entered into the multivariate logistic regression model to determine the independent risk factors for SSI.

Results
The total incidence of SSI after posterior cervical spine surgery was 4.93% (20/405). The SSI group was composed of 11 men and 9 women, whose ages ranged from 55 to 73 years (median, 65 years). The non-SSI group was composed of 232 men and 153 women, whose ages ranged from 40 to 79 years (median, 61 years). Of the 20 patients with SSI cases, super cial in 15 and deep in 5 were treated with not only prolonging the use of antibiotics but also surgical debridement and VSD covered. All patients recovered well and with no implants removed.
Univariate analysis of patient demographics revealed several signi cant predictors of SSI including patient-related risk factors, procedure-related risk factors, and perioperative factors. Several medical comorbidities were associated with SSI rates including FT, Ratio of Subcutaneous FT to MT, preoperative JOA, preoperative serum albumin. Notable factors that were not predictive of SSI included diabetes mellitus, smoking, Gender, Age, BMI, MT and so are summarized in (Table 1). Univariate and multiple logistic regression analyses were used to evaluate the effect of each factor on the SSI (Table 2). Univariate logistic regression analysis showed that subcutaneous FT, Ratio of Subcutaneous FT to MT, preoperative JOA, preoperative serum albumin, postoperative drainage, time of draining were signi cant risk factors for SSI (P < 0.05). Multivariable logistic regression analysis identi ed four positive independent predictors of SSI including Ratio of Subcutaneous FT to MT, preoperative JOA, preoperative serum albumin, time of draining. Previous studies of risk factors for SSI in Posterior cervical spine surgery on Table 3.   Discussion SSI has been found to be the most common complication in spinal surgeries serious consequences like debridement negative impact on patient-reported clinical outcomes, potential need for instrumentation removal, and increasing patient mortality. Therefore, SSI causes huge healthcare and economic burden. Previous studies have shown that the SSI rate following posterior cervical spine surgery range from 1.4%-13% higher than anterior cervical spine 5,6,19 . In our study, patients who had surgery for osteomyelitis, discitis, epidural abscess, primary or metastatic tumors were excluded due to their inherent risk of SSI. the overall rate of clinically signi cant SSI after posterior cervical spine surgery was 4.93%. the incidence of SSI reported in our study was consistent with that reported previously in the literature.
In previous reports on SSI, many estimated risk factors were reported. However, there are many debates regarding the risk factors of SSI. In this study, we performed univariate and multivariate analyses to investigate the impact of related risk factors for development of SSI. In the univariate analysis, subcutaneous FT (P < 0.001), ratio of subcutaneous FT/MT (P < 0.001), preoperative JOA Scores (P < 0.01), preoperative serum albumin (P < 0.01), postoperative drainage (P < 0.01), time of draining (P < 0.001) were identi ed as signi cant risk factors. in the multivariate logistic regression model, we entered all variables, except for those identi ed in the univariate analysis as no signi cant (P > 0.05) effects. With subsequent multivariate analysis, we were able to identify 4 independent factors ratio of subcutaneous FT/MT (P < 0.01), preoperative JOA scores (P < 0.01), preoperative serum albumin (P < 0.001), time of draining (P < 0.001) in uenced patients' risks of SSI following posterior cervical spine surgeries.
High BMI was a recognized, independent risk factor in SSI following spine surgery 11,20 . Currently, more and more studies have found that the distribution of subcutaneous fat at the site of surgery not high BMI has been previously shown to affect the risk of SSI following lumbar spine fusion, with the subcutaneous FT being an independent risk factor for infection [21][22][23] . This association has also been previously shown to increase the risk of SSI after spine surgery procedures. Obese patients are at a greater risk of SSI because of the increased the subcutaneous FT at the surgical site. The increased FT may require a longer incision, wider dissection, and increased retraction. Operative time is also increased because of the increased di culty of the surgery in these patients. As retraction is prolonged, the duration of decreased blood ow becomes longer, increasing tissue necrosis at the surgical site. Besides, redundant soft tissues and a poor wound healing environment making closure of the wound challenging, which were possible reasons for an increased risk of SSI resulting from tissue necrosis in obese patients. In the present study, the MT was not a risk factor for SSI, demonstrating that FT is at the highest risk for necrosis while MT not. Thick subcutaneous FT may allow for the development of a dead space after wound closure. This can play a role in the development of SSI following posterior cervical spine surgery. In this study, we demonstrated that the most useful predictor of incisional SSI is the ratio of FT/MT, which re ects the distribution of subcutaneous fat more accurately excluding individually in uence.
At present, the relationship between SSI following posterior cervical spine surgeries and surgical site drains is still controversial. The surgical site drain was mainly started in cervical spine surgeries to prevent the formation of epidural hematoma or seroma which may cause neurological de cit and increasing the tension on the incisions resulting in wound-related complications namely SSI and wound dehiscence 24 . Wound drain apart from supposedly aiding in SSI prevention, could cause retrograde infection, increase post-operative blood loss which increases the need for blood transfusion. In our study, drainage time was an independent risk factor for postoperative SSI. In addition, Payhs et al. 25 suggested that surgical site drains in the posterior cervical spine in combination with alcohol foam or vancomycin powder are associated with reduced odds of SSI among patients undergoing any posterior cervical spine surgery.
Current evidence demonstrates a strong and independent association between malnutrition and infectious and wound complications following posterior cervical spine surgeries 15,16 . Our results support the use of laboratory nutritional screening as a component of preoperative patient assessment and optimization to solve the di culty of assessment of nutritional status of different people. In this study, decreased preoperative serum albumin (< 3.5 g/dL) signi cantly increased the risk of postoperative SSI. Additionally, low albumin level would suppress the patients' immune function and impaired the wound healing, which increased the risk of SSI. Cooper et al. 26 reported nutritional supplementation may provide a small reduction in infections in the spine trauma population. At present, the relationship between SSI following posterior cervical spine surgeries and preoperative malnutrition is still controversial, which needs to be con rmed by multicenter and large sample randomized controlled study.
At present, there are no study on the role of preoperative JOA score in SSI. In this study, we demonstrated an interesting result that preoperative JOA score was an independent risk factor of SSI following posterior cervical spine surgery. No clinical research pointed out this view before. A poor preoperative JOA score usually suggested to denervation, pressure sores and urinary retention. In one basic research, chronically denervated tissue is more susceptible to bacterial growth and di culty in wound healing 27,28 . Poor nerve function may associate with di culty getting out of bed resulting in pressure sores, and urinary retention may result in urinary tract infection. Those several reasons may attribute to SSI following posterior cervical spine surgery.
This study didn't support for vancomycin predicting SSI possibly due to small infection rates while previous studies supported 4,29−31 . A possible theory for our results that are in contrast to those of other vancomycin studies is that local vancomycin may not have enough capacity to overcome the increased infection risk factors seen in patients undergoing fusion. Thus, the addition of other treatment modalities may be needed to prevent SSIs in the high-risk fusion population, such as improved nutrition or more stringent patient selection criteria. An additional consideration is that the current dosing of intrawound vancomycin may not be adequate, or the delivery of the medication does not last long enough in the local environment to completely control bacterial growth for these large, deep incisions.
In prior studies, DM was identi ed as a signi cant risk factor for SSI after spinal surgery 32 . However, in our study, DM was not signi cantly associated with SSI. Blood glucose were well controlled before operation, the smaller number of patients with DM, and the inclusion of several potential risk factors in the nal multivariate logistic model may have been responsible for these results. Due to the same types of surgery, the intraoperative segments are mostly 3 or 4, so the operation time is relatively close. Similarly, gender, steroid use, current smoking, history of previous SSI, estimated blood loss, and surgical procedure were not identi ed as risk factors in our study, although they have been found to be signi cant risk factors for SSI in previous studies 33 .
First, this was a retrospective nonrandomized case-control study, and the number of patients with SSI in this study was relatively small. Our study has several limitations. First, this was a retrospective nonrandomized case-control study, and the number of patients with SSI in this study was relatively small. The low rate of SSI could have prevented us from detecting correlations and statistical differences on some variables. Multicentric data pooling could help increase the included number of patients and overcome this limitation. Second, some variables that have potential to in uence the development of SSI were not included because they were not considered before the start of the study, such as type of cervical pathology, anticoagulation used, neurological outcomes, cause of death and adverse reaction to transfusion. In addition, in some cases, such as those vancomycin-related reactions, and liver disease, the sample size was too small to allow investigation of their effects on SSI occurrence. Owing to these limitations, high-quality observational studies and basic experimental studies are still needed to investigate new risk factors for SSI further in the future.

Conclusions
A total of 20 SSIs (4.93%) occurred in 405 cases of posterior cervical spine surgeries. Incidence of SSI signi cantly prolonged hospitalization, increased hospitalization expenses. Ratio of subcutaneous FT to MT, preoperative JOA score, preoperative serum albumin and longer time of draining were found to be signi cantly associated with SSI after posterior cervical spine surgeries. Identi cation of these risk factors for SSI could be of great value in risk-bene t analysis of prophylaxis after posterior cervical spine surgeries, and adequate management of preoperative risk to reduce SSI incidence. In addition, the results could be used in counseling patients and their families during the consent process. Method used to measure the MT, subcutaneous FT, and lamina at skin surface at the C5 level using sagittal views as determined on T2-weighted magnetic resonance imaging.