Although large-scale efforts have been initiated to help mitigate postoperative SSIs after lumbar spinal surgery, associated morbidity remains high. The incidence of spinal SSI ranges from 0.7–16%, depending on the type of surgery and the area involved 2,3. A postoperative course complicated by SSI may require long and repeated hospitalizations and multiple surgical interventions, including irrigation and debridement, hardware removal, and complex wound closure. Early diagnosis and treatment greatly improve patient outcomes and shorten the time to recovery.
SSI is typically diagnosed by a surgeon or based on the assessment of images [e.g. computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)]. Other indicators, such as clinical laboratory markers, are also of great value in predicting and monitoring SSI13 − 15because of their objectivity, low cost, and convenience12,16.
The biochemical markers used most widely for the early diagnosis of SSI are CRP, ESR, total WBC count, and differential WBC count. Several studies have reported the usefulness of these biomarkers and found that the combined use of normal CRP, ESR, and WBC levels reliably predicts the absence of infection after lumbar spinal surgery14.15Changes in ESR and CRP after surgery may be used to distinguish between infected and non-infected patients. Larsson et al.17 were the first to report changes in CRP level after lumbar posterior surgery; the authors observed that CRP level returned to baseline (< 10 mg/L) within 21 days after surgery. However, Takahashi et al18. reported that postoperative CRP level peaked on day 2, and Aono et al.19reported that CRP level peaked on day 4. Postoperative CRP levels peaked between POD2 and POD4. Iwata et al.16 reported that a CRP level > 10 mg/dL at 4 days postoperatively was useful for the definitive diagnosis of SSI. Kyu et al.20 reported that the observation of abnormal CRP levels three days postoperatively should cause the clinician to be highly suspicious of infection.
It is believed that CRP levels remain elevated or increase further at POD4, suggesting that SSI is more likely to occur. 16.18.22The results showed that the level of CRP had increased significantly on POD 3 in the SSI group and remained high on POD7. In the non-SSI group, CRP levels had increased significantly on POD3, then decreased slightly by POD7 (Fig. 1D). In both the SSI and the non-SSI group, ESR levels had increased significantly at POD3, but were then observed to have decreased slightly on POD7 (Fig. 1E). ESR increased to peak levels at POD5, followed by a slow and irregular decreasing trend17. Therefore, CRP appears to be more suitable than ESR for evaluating infection.
Our results showed that CRP levels had increased in all patients on POD1. In non-SSI patients, decreases in CRP levels were observed on POD3 and POD7. However, in the SSI group, CRP levels were higher on POD3 and decreased on POD7. We determined the diagnostic cutoff for CRP by using the ROC curve. If CRP levels are > 26 mg/dL on POD7, infection should be highly suspected, and the antibiotic regimen should be changed or increased in dose.
Several factors have been reported to affect postoperative CRP levels. These factors include blood loss, preoperative CRP levels, and the segment on which spinal surgery was performed. For example, surgery in the lumbar region is associated with higher postoperative CRP levels than surgery in other areas. 21. Given the uncertainty of the use of CRP as a diagnostic tool for SSI, additional laboratory predictors are needed to distinguish between infected and non-infected patients at the postoperative stage.
WBC counts and lymphocyte counts were first reported to be helpful for the early diagnosis of surgical wound infections after lumbar surgery by Takahashi et al. 22 Takahashi et al. found that lymphocyte ratio ≤ 10% or count < 1,000/ µL at POD4 were associated with increased risk for surgical wound infection. The authors suggest that lymphocytopenia represents an immunosuppressive state. This increase in the body's susceptibility to infection may lead to the development of postoperative infection. Subsequent studies supported these claims. Iwata et al. showed that a lymphocyte count < 1,000/µL at POD4 was the only significant independent laboratory marker for the early detection of SSI 16. Furthermore, Chao-Jun Shen et al. reported 23 that neutrophil/lymphocyte count ratio (NLR) at POD4 and POD7 was a valuable marker for SSI in patients who had recently undergone posterior lumbar spinal surgery. When ROC results were analyzed for NLR > 5.19 at POD4, the sensitivity and specificity of the NLR were 61.5% and 77.6%; the AUC was 0.708. For NLR > 3.85 at POD7, sensitivity and specificity were 69.2% and 62.7%; the AUC was 0.663. The cutoff for the percentage of lymphocytes at POD4 was < 15%; sensitivity of this marker was 61.5%, and specificity was 73.3% (AUC = 0.682).
Our results showed that, in all patients, neutrophil count increased and lymphocyte count decreased on POD1. In non-SSI patients, neutrophil count began to decrease on POD3, which is also when lymphocyte count began to increase. However, in infected patients, a further increase in neutrophil count and decrease in lymphocyte count were detected on POD3 (Fig. 1B,C). We therefore chose to determine the diagnostic cutoff for lymphocyte ratio using the ROC curve. If lymphocyte ratio was less than 11.5% at POD3, infection was highly suspected, as in studies performed previously. We believe that POD4 lymphocyte count is more useful than POD7 lymphocyte count because the data can be obtained earlier during the course of postoperative recovery. POD4 lymphocyte count appears to be an important indicator of SSI after posterior lumbar surgery.
In this study, we analyzed the sensitivity and specificity of five laboratory markers for the early detection of SSI. Two laboratory markers were found to have acceptable levels of sensitivity and specificity. The first indicator was CRP level > 26 mg/dL on day 7 after surgery. For this marker, sensitivity and specificity were 90.9% and 87.7%, respectively, and the AUC was 0.954. The other indicator was lymphocyte ratio < 11.50% on the third day after surgery. For this marker, sensitivity and specificity were 90.9% and 75.4%, respectively, and the AUC was 0.919. If the lymphocyte ratio was < 11.50% on POD 3, or the CRP level is > 26 mg/dL on POD 7, clinicians should check the surgical wound more carefully. If necessary, imaging diagnostic tools such as CT and MRI may be used.
Our research has several limitations. First, this was a retrospective study. Therefore, there may be inherent bias associated with patient selection and missing patient information. Second, chronic SSI patients may have been included in the non-SSI group. Patients were assigned to groups based on the results of the hospitalization exam. The actual number of SSI cases may therefore have been underestimated. In future studies, we will expand the study population as well as the duration of follow-up.