Effect of Preoperative Epidural Spinal Injections on Complications After Posterior Lumbar Interbody Fusion

Abstract

Study Design

Retrospective Cohort study.

Objective

To examine whether preoperative epidural spinal injections (ESI) is associated with postoperative infection, dural leak, or nerve injury following posterior lumbar interbody fusion (PLIF).

Methods

The PearlDiver database was used to identify adults aged 18-85 who underwent a PLIF procedure between 2016 and 2022. Only patients that received an ESI up to three years prior to the PLIF were included. Complications were excluded if they occurred more than 120 days after PLIF. Chi-squared tests were performed for statistical analyses on the entire cohort pooled across years.

Results

A total of 172,422 patients met inclusion criteria, of which 9,740 (5.6%) received a preoperative ESI. The incidence of postoperative infection was significantly higher in the overall injection cohort compared with patients without prior injection (OR 1.38, 95% CI 1.22-1.53, p < 0.0001). When stratified by timing, ESIs administered within 3 years (OR: 1.29, p = 0.003), 1 year (OR: 1.37, p = 0.027), 6 months (OR: 1.48, p = 0.016), and 6 weeks (OR: 1.62, p = 0.029) before surgery were each associated with higher postoperative infection risk. No statistically significant differences were observed in dural leak incidence between injection and no-injection patients (p = 0.83). Pre-operative ESI was associated with greater odds of nerve injury (OR: 1.75, p =0.047).

Conclusion

PLIF performed after ESI is associated with modestly increased risk of infection and nerve injury. Shorter time from ESI to PLIF is associated with higher rates of infection.

Introduction

Preoperative epidural steroid injections (ESIs), including interlaminar, transforaminal, and caudal approaches, are commonly used to treat lumbar radiculopathy, spinal stenosis, and degenerative disc disease, and have demonstrated efficacy in providing symptomatic relief.^1-3 ESIs exert their effects by suppressing inflammatory cytokines and modulating cellular immune responses, which may improve pain but also potentially increase the risk of complications such as infection, dural leak, and nerve injury through attenuation of the native immune response.^4,5

Although ESIs are effective for short-term symptom control and may delay surgical intervention, growing concern exists regarding their impact on postoperative outcomes following lumbar spine surgery. Prior studies suggest that the timing of ESI administration relative to surgery may influence the risk of postoperative complications, including surgical site infection, dural tear, and cerebrospinal fluid (CSF) leak.^6-8 Large database analyses of lumbar fusion procedures have demonstrated an increased risk of postoperative infection when surgery is performed within 30 days of an ESI, with diminishing risk between one and three months and no observed effect beyond three months.^7,9 Additionally, several studies have reported an association between preoperative ESIs and increased rates of dural leak in patients undergoing minimally invasive lumbar discectomy, single-level lumbar decompression, and transforaminal lumbar interbody fusion.^10-13

Interpretation of the existing literature is limited by heterogeneity in surgical procedures, which may confound complication rates. To mitigate this limitation, the present study focuses exclusively on patients undergoing posterior lumbar interbody fusion (PLIF), thereby reducing variability related to surgical type and extent. Furthermore, the relationship between preoperative ESIs and postoperative nerve injury remains poorly defined. This study aims to evaluate whether patients receiving preoperative ESIs prior to PLIF experience higher rates of postoperative infection, dural leak, or nerve injury compared with patients who did not receive injections, using a large national database. A secondary objective is to assess the effect of time interval from ESI to PLIF on postoperative infection rates. We hypothesize that preoperative ESIs are associated with increased rates of postoperative infection, dural leak, and nerve injury, and that shorter time intervals between ESI and surgery confer a higher risk of infection.

Methodology

The data for this investigation was sourced from PearlDiver Inc., an insurance-based nationwide database, which includes a longitudinal cohort of 170 million distinct patients. The data queried for this study encompassed the years 2016 to 2022 and included all adults aged 18-85. Due to the nature of the de-identified patient database, institutional review was not necessary.

This study utilized a retrospective cohort design to evaluate whether patients who received posterior lumbar interbody fusion (PLIF) surgery and had fluoroscopic guidance for an injection developed infections, dura-leaks, or nerve injuries post operation. PLIF surgeries were identified using Current Procedural Terminology (CPT) codes 22630 and 22633 indicating single level fusion. Only patients that received an injection three years prior to the PLIF were included. Injections were identified using CPT codes 62322 and 62323 and were administered using fluoroscopic guidance for placement (CPT-77003).Infections were identified by International Classification of Disease (ICD) 10 Diagnosis codes T8142XA, T8143XA, T8149XA and T814XX; dural tear and postprocedural air leaks with ICD codes J95812 and G9611; and nerve root injuries of the lumbar spine, sacral spine, or cauda equina with ICD codes S3421XA, S3421XD, S3421XS, S3422XA, S3422XD, S3422XS, S343XXA, S343XXD, S343XXS, and G9781. All outcomes were excluded if they occurred more than 120 days after PLIF surgery to ensure they were due to surgery and no other procedures.

To determine whether preoperative injection exposure timing influenced postoperative complication risk, further analyses were stratified by the length of time between the most recent injection and the PLIF procedure. Patients were grouped into injection timing categories of 3 years, 1 year, 6 months, and 6 weeks prior to PLIF. Patients that underwent PLIF without any injection in the three years prior to the surgery served as the reference group. Secondary analyses separated injection exposure into recent (<6 months before PLIF) versus remote (>6 months to 3 years before PLIF) to evaluate threshold effects of injection proximity on postoperative outcomes. Separate analyses were conducted to determine if number of injections (1, 2, or >2) preoperative to PLIF surgery had any association with outcomes. However, low numbers of patients that received multiple injections limited statistical analysis.

Chi-squared tests were performed for statistical analyses on the entire cohort pooled across years. Results for categorical outcomes were reported as odds ratios with 95% confidence intervals. All statistical procedures were conducted using PearlDiver’s R package.

Results

This study cohort consisted of 172,422 patients who underwent PLIF, of which 9,740 (5.6%) received a preoperative ESI. The incidence of postoperative infection was found significantly higher in the injection group (3.17%) compared to the no-injection group (2.32%) (Absolute Risk Difference 0.85%, OR 1.38, 95% CI 1.22-1.53, p < 0.0001). There was no significant difference in dural leak incidence (0.21% vs 0.19%, p = 0.8269). The incidence of nerve injury was also higher in the injection group (0.16% vs .09%, OR 1.75, 95% 1.04-2.93, p = 0.0472) (Table 1).

Table 1.

Chi-Square Analysis of Preoperative Epidural Spinal Injection on Postoperative Complications

​	Injection (n = 9740)	No-injection (n = 162682)	Odds ratio (95% CI)	p value
Infection	309 (3.17%)	3780 (2.32%)	1.38 (1.22-1.55)	< 0.0001
Dural Leak	20 (0.21%)	309 (0.19%)	1.08 (0.69-1.70)	0.8269
Nerve Injury	16 (0.16%)	153 (0.09%)	1.75 (1.04-2.93)	0.0472

Of those who received an ESI preoperatively, 5,096 (52.3%) had it between 3 years and 1 year before surgery, 1,737 (17.8%) between 1 year and 6 months before surgery, 2,260 (23.2%) between 6 months and 6 weeks before surgery, and 647 (6.6%) within 6 weeks before surgery (Figure 1). All ESI time windows were associated with a significantly higher postoperative infection rate compared to those who did not receive an injection (Figure 2). As the time window between ESI and surgery decreased, the odds ratio for postoperative infection increased with the highest ratio in those receiving a preoperative ESI within 6 weeks of surgery (3.71%, OR 1.62, 95% CI 1.08–2.44, p = 0.0197) (Table 2). Because of low incidence of nerve injury, we could not demonstrate time-interval dependent variability relationship between the ESI and nerve injury.

Figure 1.

Distribution of preoperative epidural Steroid injections by timing

Figure 2.

Postoperative infection rate by preoperative ESI timing

Table 2.

Chi-Square Analysis of Preoperative Epidural Spinal Injection Timing on Postoperative Infection

Time window	Infection (%)	Odds ratio (95% CI)	p value
No - Injection	3780 (2.32%)	1.00	---
3 Years – 1 Year Preoperatively	152 (2.98%)	1.29 (1.10-1.52)	0.0022
1 Year – 6 Months Preoperatively	55 (3.17%)	1.37 (1.05-1.80)	0.0206
6 Months – 6 Weeks Preoperatively	78 (3.45%)	1.50 (1.20-1.89)	0.0004
6 Weeks Preoperatively	24 (3.71%)	1.62 (1.08-2.44)	0.0197

Discussion

The principal findings of this study are twofold: first, preoperative ESIs are associated with increased rates of postoperative infection and nerve injury following PLIF, but not with higher rates of dural tear; and second, shorter intervals between ESI administration and PLIF are associated with an increased risk of postoperative infection. While prior studies have evaluated the impact of preoperative ESIs on outcomes after spine surgery, this study is, to our knowledge, the first to specifically examine their association with postoperative complications following PLIF. Several studies have reported on the effect of ESI’s on complications after spine surgery, but include multiple operations that have various indications for degeneration and instability, such as fusion alone versus addition of interbody device, which can introduce confounders.^7,14 By restricting the analysis to a single surgical procedure, we aimed to reduce procedural heterogeneity and more precisely attribute observed effects to preoperative ESI exposure. Additionally, the use of a large, nationwide insurance-based database enhances the generalizability of our findings and provides sufficient statistical power to conduct time-dependent analyses and detect clinically meaningful differences.

There are several mechanisms as to how pre-operative ESIs may contribute increased complications after PLIF. Due to the immunosuppressive effects of steroids, ESI can result in local immunosuppressive where administered that eventually wears off, explaining the time-dependent infection risk between pre-operative ESIs and PLIF.^7,8,15 Additionally, there is a risk of direct contamination with skin flora.^7,9,16 ESI’s may also increase the risk of epidural scarring and reduction in fibroblast activity making the dura more susceptible to injury.^11,17

With respect to postoperative infection, our study demonstrated a significantly higher incidence in the injection group compared with the no-injection group (OR 1.38, 95% CI 1.22–1.53; p < 0.0001). The overall infection rate was 3.17% in patients who received preoperative ESIs, compared with 2.32% in those without prior injections, a difference that was statistically significant. These findings are consistent with prior reports in the literature.

In patients undergoing lumbar fusion surgery, Singla et al reported infection rates of 3.9% (66 of 1,699) among patients who received an ESI within one month of surgery and 2.2% (120 of 5,491) among those who received an ESI within one to three months preoperatively. ⁷ Similarly, Zusman et al found that preoperative epidural spinal injections were associated with a 7.4-fold increase in surgical wound complications in patients undergoing lumbar and thoracolumbar arthrodesis, although overall complication rates and short-term patient-reported outcomes were not significantly different. ¹⁸ Moreover, a recent 2024 systematic review and meta-analysis found that pre-operative ESIs increased the risk of post-operative infection after cervical and lumbar spinal surgery, with a number needed to harm of 111 making the benefits of pre-operative ESIs outweigh the risks. ¹⁹ Similarly, this study found a statistically significant increase of infection rate from 3.17% for patient receiving a pre-operative ESI compared to 2.32% for those without. However, given the small absolute difference, it remains unclear whether this is clinically significant. Based on this study’s results with a number needed to harm of 118, ESIs may remain safe in many contexts.

Collectively, these findings support robust evidence that ESIs represent a risk factor for postoperative infection. While ESIs provide effective, targeted pain relief, their anti-inflammatory effects may impair host immune defenses by altering neutrophil, macrophage, monocyte, and plasma cell function.^4,5,20 In addition to the potential for bacterial inoculation during needle penetration of the skin, these immunomodulatory effects likely contribute to the increased infection risk observed in patients receiving ESIs prior to PLIF. ⁵ Furthermore, ESIs may promote epidural fibrosis, potentially increasing operative difficulty and prolonging surgical time required to access the disc space during PLIF, which may further contribute to postoperative infection risk.

This study also demonstrated that shorter intervals between ESI administration and PLIF were associated with higher postoperative infection rates, with the greatest risk observed when ESIs were administered within six weeks preoperatively (OR 1.62, 95% CI 1.08–2.44; p = 0.0197). Khalid et al reported that ESIs administered within 30 days of lumbar decompression increased the risk of cerebrospinal fluid leak but were not associated with higher infection rates. ⁶ In contrast, a 2023 systematic review and meta-analysis found that ESIs performed within one month of cervical or lumbar spine surgery were associated with an increased risk of postoperative infection. ¹⁵

Overall, the findings of the present study are consistent with existing literature; however, the optimal timing for safely performing PLIF after ESI remains uncertain. Appropriate surgical timing is likely patient-specific and influenced by individual comorbidities and risk tolerance.^21,22 Notably, a minimum interval of three months between corticosteroid injection and surgery is commonly recommended for patients undergoing shoulder, hip, and knee arthroplasty, suggesting a potential framework that may warrant consideration in spine surgery.^23-25 Further individual risk assessment and prospective studies are necessary to establish a safe duration between ESIs and PLIF.

Our study demonstrated that there was no significant difference in dural leak in patients undergoing PLIF procedures, with an incidence (p = 0.8269). The literature remains sparse on dural leaks in the setting of ESI injection prior to PLIF procedures specifically. Shakya et al found that in patients undergoing minimally invasive lumbar discectomy, receiving an ESI within 3 months of surgery was a statistically significant risk factor for dural tear. ¹¹ However, PLIF can be performed with both minimally-invasive and open techniques with a noted elevated risk of baseline dural tear that can confound the results.^26,27 Additionally, our study did not seek to establish a timing-dependent association. There was no significant difference in dural leak during PLIF after ESI, with twenty patients (0.205%) developing a dural leak during PLIF in the injection group and 306 patients (0.190%) in the no-injection group. The difference in the results across studies analyzing dural leak risk is likely due to overall low incidence of dural leaks and patient populations. Additionally, there are numerous confounding patient and surgeon specific factors, as well as type, location, and number of injections that can influence results.

Nerve injury is a rare complication of both ESIs and PLIF. In this study, however, patients who underwent PLIF following preoperative ESI demonstrated a higher incidence of postoperative nerve injury, although only 169 patients could be included in the analysis. Specifically, 16 patients (0.164%) in the injection group experienced a nerve injury, compared with 153 patients (0.094%) in the no-injection group (OR 1.75, 95% CI 1.04–2.93; p = 0.047). One proposed mechanism is that ESIs may lead to epidural scarring and adhesions, thereby increasing the risk of iatrogenic nerve injury during PLIF as a result of more extensive neurolysis. ¹⁸ The low overall incidence of nerve injury limited the ability to perform a time-interval analysis, precluding assessment of a time-dependent relationship between ESI exposure and nerve injury similar to that observed for postoperative infection.

This study has several limitations. While this nationwide dataset offers a large sample size resulting in increased generalizability and power, there is less granularity regarding details of the ESI, PLIF, and complications. For example, the impact of variables such as location of ESI, number of levels fused during PLIF, type of steroid use, and degree of nerve injury (neuropraxia vs neurotmesis) could not be evaluated. Due to low overall numbers for patients receiving multiple injections, separate statistical analyses for complications based on number of injections could not be performed. Additionally, the effect of comorbidities such as diabetes, smoking, immunosuppression, etc. could not be accounted for and are potential confounders, as well as the fact that patient receiving ESI’s may have more severe or persistent symptoms resulting in selection bias. Further limitations to our study include lack of information on operation time, blood loss, and surgical techniques being open or minimally invasive which are known contributors to infection risk. Due to being a database study, we could not capture data on indication for ESI, severity of disease, and primary versus revision surgery. As data from healthcare centers across the United States were gathered, there is variability in institution-specific guidelines for sterility and training for administering ESIs that could influence the results. As with any database study relying on ICD and CPT codes, it is possible that patients were coded incorrectly and therefore missed during the analysis. Moreover, the true incidence of dural tears may be lower than reported in this study as they can be repaired intra-operatively and underreported. This would be especially true for dural leak as those dural tear which is primarily repaired at the time of the surgery may not be reported. Nevertheless, this study offers insight into the impact and timing of ESIs on complications after PLIF. The results can guide surgeons and inform patients being treated for spinal conditions who may receive ESIs, particularly those who may receive PLIF in the future. Future research ought to determine a safe timing window for when it is appropriate to undergo PLIF after an ESI, as well as the effect of multiplicative risk factors such as immunocompromising conditions, smoking, and diabetes on complications.

Conclusion

PLIF performed after ESI is associated with modestly increased risk of infection and nerve injury. Shorter time from ESI to PLIF is associated with higher rates of infection.

ORCID iDs

Varun Gopinatth https://orcid.org/0000-0002-6127-1221

Jonathan Kark https://orcid.org/0000-0003-0363-401X

Jung U. Yoo https://orcid.org/0000-0001-7002-7151

Ethical Considerations

This study was deemed exempt from Institutional Review Board review.

Consent to Participate

Informed consent was not necessary or obtained for this study.