- 2021;24;41-59Is Epidural Injection of Sodium Chloride Solution a True Placebo or an Active Control Agent? A Systematic Review and Meta-Analysis
Laxmaiah Manchikanti, MD, Nebojsa Nick Knezevic, MD, PhD, Jaya Sanapati, MD, Alan D. Kaye, MD, PhD, Mahendra R. Sanapati, MD, and Joshua A. Hirsch, MD.
BACKGROUND: Epidural injections have been extensively used since their description in 1901, and steroids since their first utilization in 1952. Multiple randomized controlled trials and systematic reviews have reached discordant conclusions regarding the effectiveness of sodium chloride solution and steroids in managing spinal pain.
True placebo-controlled trials with the injection of an inactive substance to unrelated structures have been nonexistent. Consequently, the discussions continue to escalate, seemingly without proper discourse.
In this review, we sought to assess the true placebo nature of saline and the effectiveness of steroids.
OBJECTIVES: This assessment of sodium chloride solution is undertaken to assess if it is a true placebo when injected into the epidural space, is effective alone, and whether steroids are effective when injected with sodium chloride solution rather than local anesthetic in managing spinal pain.
STUDY DESIGN: A systematic review of randomized controlled trials utilizing sodium chloride solution alone, steroids alone, or sodium chloride solution with steroids in managing spinal pain secondary to disc herniation or spinal stenosis.
METHODS: The systematic review was performed utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Cochrane review criteria and Interventional Pain Management techniques--Quality Appraisal of Reliability and Risk of Bias Assessment (IPM–QRB) was used to assess the methodological quality assessment. Qualitative analysis was performed by utilizing best evidence synthesis principles, and quantitative analysis was performed utilizing meta-analysis with conventional methodology and single-arm meta-analysis.
PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1966 through December 2018. The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5.
Outcome measures for the present analysis, 20% improvement from the baseline pain scores or disability scores was considered clinically significant. Effectiveness was determined short-term if it was less than 6 months, whereas longer than 6 months was considered to be long-term.
RESULTS: Of the 8 trials meeting inclusion criteria, 2 trials utilized fluoroscopic imaging and one study utilized ultrasound. All other studies performed the procedure without fluoroscopy.
With dual-arm meta-analysis, there was no significant difference between epidural sodium chloride solution and epidural steroids with sodium chloride solution. Utilizing single-arm analysis, both epidural saline and epidural steroids with saline were effective in reducing 20% of pain, however, only reducing disability scores by 10% to 12%.
Based on the qualitative analysis, epidural saline and epidural steroids with saline showed effect beyond placebo and showed level I, or strong evidence, that neither epidural saline, nor epidural steroids with saline are placebo and that both are effective.
LIMITATIONS: Despite 8 randomized controlled trials, only 2 of them utilized fluoroscopy. Overall evidence is considered less than optimal and further studies elucidating these actions are strongly recommended.
CONCLUSIONS: The findings of this systematic review and meta-analysis show that epidurally administered sodium chloride solution and sodium chloride solution with steroids may be effective in managing low back and lower extremity pain. Consequently, the findings of this review provide information that epidurally administered sodium chloride solution is not a true placebo.
KEY WORDS: Chronic low back pain, epidural injections, local anesthetic, sodium chloride solution, steroids, placebo effect