- Medical Director of the Pain Management Center of Paducah, 2831 Lone Oak Road, Paducah, KY, 42003, and Clinical Professor, Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY, USA
- Rehabilitation Medicine, New York University School of Medicine, New York, NY, USA
- Fourth Year Resident in Department of Physical Medicine and Rehabilitation at the University of Kentucky, Lexington, KY, USA
- Medical Director of Mid Atlantic Spine and Pain Physicians, Newark, DE, Pain Medicine Fellowship Program, Temple University Hospital, Philadelphia, PA, Department of PM and R, Temple University Medical School, Philadelphia, PA, USA
- Medical Director, Spine Pain Diagnostics Associates, Niagara, WI, USA
- Medical Director, Millennium Pain Center, Bloomington, IL, and Clinical Assistant Professor of Surgery, College of Medicine, University of Illinois, Urbana-Champaign, IL, USA
- Department of Anesthesia, LSU Health Science Center, New Orleans, LA, USA
- Interventional Pain Program, Professor and Director Pain Fellowship, Department of Orthopedics and Rehabilitation Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
- Ohio Pain Clinic, Centerville, OH, USA
- Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA., USA
- 0President of Manhattan Spine and Pain Medicine, Department of Anesthesiology, NYU Langone-Hospital for Joint Diseases, NYU School of Medicine, New York, NY, USA
- 1Medical Director of Pain Medicine and Associate Professor of Anesthesiology and Orthopedics, Department of Anesthesiology, NYU Langone-Hospital for Joint Diseases, NYU School of Medicine, New York, NY, USA
- 2Department of Anesthesia, Critical Care, and Pain Medicine at Beth Israel Deaconess Medical Center, Boston, MA, and Assistant Professor of Anesthesiology at Harvard Medical School, Harvard Medical School, Boston, MA, USA
- 3Vice Chief of Interventional Care, Chief of Minimally Invasive Spine Surgery, Service Line Chief of Interventional Radiology, Director of Endovascular Neurosurgery and Neuroendovascular Program, Massachusetts General Hospital; and Associate Professor, Department of Radiology, Harvard Medical School, Boston, MA, USA
Correspondence Address:
Laxmaiah Manchikanti
3Vice Chief of Interventional Care, Chief of Minimally Invasive Spine Surgery, Service Line Chief of Interventional Radiology, Director of Endovascular Neurosurgery and Neuroendovascular Program, Massachusetts General Hospital; and Associate Professor, Department of Radiology, Harvard Medical School, Boston, MA, USA
DOI:10.4103/2152-7806.156598
Copyright: © 2015 Manchikanti L. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.How to cite this article: Manchikanti L, Nampiaparampil DE, Manchikanti KN, Falco FJ, Singh V, Benyamin RM, Kaye AD, Sehgal N, Soin A, Simopoulos TT, Bakshi S, Gharibo CG, Gilligan CJ, Hirsch JA. Comparison of the efficacy of saline, local anesthetics, and steroids in epidural and facet joint injections for the management of spinal pain: A systematic review of randomized controlled trials. Surg Neurol Int 07-May-2015;6:
How to cite this URL: Manchikanti L, Nampiaparampil DE, Manchikanti KN, Falco FJ, Singh V, Benyamin RM, Kaye AD, Sehgal N, Soin A, Simopoulos TT, Bakshi S, Gharibo CG, Gilligan CJ, Hirsch JA. Comparison of the efficacy of saline, local anesthetics, and steroids in epidural and facet joint injections for the management of spinal pain: A systematic review of randomized controlled trials. Surg Neurol Int 07-May-2015;6:. Available from: http://surgicalneurologyint.com/surgicalint_articles/comparison-efficacy-saline-local-anesthetics/
Abstract
Background:The efficacy of epidural and facet joint injections has been assessed utilizing multiple solutions including saline, local anesthetic, steroids, and others. The responses to these various solutions have been variable and have not been systematically assessed with long-term follow-ups.
Methods:Randomized trials utilizing a true active control design were included. The primary outcome measure was pain relief and the secondary outcome measure was functional improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the criteria developed by the American Society of Interventional Pain Physicians (ASIPP) for assessing interventional techniques. An evidence analysis was conducted based on the qualitative level of evidence (Level I to IV).
Results:A total of 31 trials met the inclusion criteria. There was Level I evidence that local anesthetic with steroids was effective in managing chronic spinal pain based on multiple high-quality randomized controlled trials. The evidence also showed that local anesthetic with steroids and local anesthetic alone were equally effective except in disc herniation, where the superiority of local anesthetic with steroids was demonstrated over local anesthetic alone.
Conclusion:This systematic review showed equal efficacy for local anesthetic with steroids and local anesthetic alone in multiple spinal conditions except for disc herniation where the superiority of local anesthetic with steroids was seen over local anesthetic alone.
Keywords: Chronic pain, epidural injections, facet joint injections, local anesthetic, spinal pain, steroids, saline
INTRODUCTION
The increasing prevalence of spinal pain and disability, and the explosion of health care costs are major issues for the US and the world.[
Martin et al.[
In another manuscript, Manchikanti et al.[
Epidural injections are used in managing spinal pain secondary to disc herniation, spinal stenosis, postsurgery syndrome, discogenic pain not from facet or sacroiliac joints, and multiple other conditions.[
The response to epidural injections is variable for various pathologies including disc herniation and/or radiculitis, discogenic pain without disc herniation, spinal stenosis, and postsurgery syndrome. Manchikanti et al.,[
Steroids and local anesthetics have multiple mechanisms of action when injected into the epidural space; antiinflammatory effects are predominantly seen with steroids and other effects are seen with local anesthetics.[
This systematic review assesses randomized controlled trials of epidural and facet joint injections utilizing saline, local anesthetic, and/or steroids. The objective of this review is to characterize the role of saline and local anesthetic in these procedures and to compare their effects to those of steroids in the long-term.
METHODS
The methodology for this systematic review was derived from evidence-based systematic reviews and meta-analyses of randomized trials.[
Only randomized trials utilizing a true active control design with injection of either sodium chloride solution or local anesthetic or steroid into the epidural space, on the nerve root, in the joint, or facet joint nerves were included. True placebo injections, that is, injections of inactive solutions into inactive structures, were not included.
In active control trials, two different procedures or drugs are compared. For this assessment, only the trials comparing sodium chloride solution, local anesthetic, or steroids were utilized. The rationale for assessing only the aforementioned agents is that they are the most clinically relevant medications. Further, trials where a drug was injected outside the epidural space, nerve root, or joint were excluded. This evidence will address the misconception concerning local anesthetic as a placebo or even sodium chloride solution as a pure placebo.
The interventions evaluated were caudal and interlaminar epidural injections in the cervical, thoracic, and lumbar regions; transforaminal epidural injections in the cervical, thoracic, and lumbar regions; and facet joint injections and nerve blocks in the cervical, thoracic, and lumbar regions.
The primary outcome measure was pain relief; the secondary outcome measure was functional improvement. A literature search was performed from various resources including PubMed, the Cochrane Library, the US National Guideline Clearinghouse (NGC), previous systematic reviews, and cross references.
The search period covered from 1966 through March 2014.
The search strategy emphasized chronic neck, thoracic, low back, and upper extremity pain; lower extremity pain; and chest wall pain treated with epidural or facet joint interventions. Search terms were:
(Chronic low back pain or chronic back pain or chronic neck pain or disc herniation or discogenic pain or facet joint pain or herniated lumbar discs or nerve root compression or lumbosciatic pain or postlaminectomy or lumbar surgery syndrome or radicular pain or radiculitis or sciatica or spinal fibrosis or spinal stenosis or zygapophyseal) and (epidural injection or epidural steroid or epidural perineural injection or interlaminar epidural or intraarticular corticosteroid or nerve root blocks or intraarticular injection or periradicular infiltration or saline injection or transforaminal injection or corticosteroid or methylprednisolone or facet joint or medial branch block); Sort by: Publication Date; Filters: Clinical Trial, Controlled Clinical Trial, Evaluation Studies, Multicenter Study, Randomized Controlled Trial, Validation Studies, Comparative Study.
The quality of each individual article was assessed for bias using Cochrane review criteria [
The literature search, selection of trials, and methodological quality assessment were performed by at least two authors for each task. The allocation of trials for methodological quality assessment was distributed among the authors. Any discrepancies were resolved by consensus and the primary (LM) and senior (JH) authors.
Trials scoring 8–12 on Cochrane review criteria or 32–48 on ASIPP criteria were considered high quality, trials scoring 4–7 on Cochrane review criteria or 20–31 on ASIPP criteria were considered moderate quality, and studies scoring less than 4 on Cochrane review criteria or less than 20 on ASIPP criteria were considered low quality.
A meta-analysis was conducted if there were more than two trials that were condition-specific and homogeneous.
Analysis of the evidence was based on the condition, region, and modality (e.g. lumbar disc herniation, cervical spinal stenosis, or thoracic facet joint arthritis) so as to reduce any clinical heterogeneity.
The summary measure for pain was a 50% or more reduction of pain in at least 50% of the patients, or at least a 3-point decrease in pain scores; for disability scores the summary measure was a 50% or more reduction in disability in at least 40% of the patients or at least a 30-point decrease in disability scores measured on a scale of 0–100.
The analysis of evidence was conducted based on the qualitative level of evidence criteria synthesized by ASIPP[
RESULTS
The literature search and study selection is shown in
Meta-analysis
There was no homogeneity among the 31 trials meeting the inclusion criteria for methodological quality assessment when the region, technique, solutions injected, and use of fluoroscopy were considered. Of the 31 trials, 13 trials by Manchikanti et al. assessing the role of epidural injections were similar in many aspects;[
Study characteristics
Study characteristics and outcomes are described in
Caudal epidural injections
Among those trials meeting the inclusion criteria, there were six examining the efficacy of caudal epidural injections with multiple solutions.[
Four of these studies were conducted by Manchikanti et al.[
All four trials showed similar results for the efficacy of caudal epidural injections with local anesthetic alone or local anesthetic with steroids in 50–80% of the patients. In these trials, success was defined as at least 3 weeks of significant improvement (50% improvement) in pain and function after the first two injections. All patients were grouped into successful (responsive) or nonresponsive categories accordingly. We then calculated the number of patients with disc herniation, discogenic pain, spinal stenosis, or postsurgery syndrome who were nonresponsive to local anesthetic alone or local anesthetic with steroid. We observed no significant differences in the patients who did not respond to either injection for any of the spinal conditions. This suggests that none of the spinal conditions influenced the response to either type of injection.
The study by Sayegh et al.[
Iversen et al.,[
In conclusion, there was Level I evidence supported by multiple, relevant high-quality randomized controlled trials[
There was also Level I evidence, based on multiple, relevant high-quality randomized controlled trials,[
Lumbar transforaminal epidural injections
There were eight randomized controlled trials assessing the efficacy of multiple solutions used in lumbar transforaminal administration.[
Cohen et al.,[
Ghahreman et al.,[
In a large trial, Karppinen et al.[
Nam and Park[
Manchikanti et al.,[
Riew et al.,[
Ng et al.[
Tafazal et al.[
There was Level I evidence, based on multiple, relevant high-quality randomized controlled trials,[
There was Level II evidence, based on one high-quality trial, that local anesthetics with steroids are superior to local anesthetic alone in avoiding surgery (33% vs 71%),[
Lumbar interlaminar epidural injections
There were six randomized controlled trials assessing the efficacy of multiple solutions used in lumbar interlaminar epidurals.[
Three of these studies were conducted by Manchikanti et al.[
In these manuscripts, the study subcategories were identified as responsive and nonresponsive groups. The responsive groups consisted of patients who received at least 3 weeks of significant improvement (50% improvement) in pain and function with the first two procedures. The number of patients in the nonresponsive category who received interlaminar epidural injections of local anesthetic only included 10 who had disc herniation, five who had discogenic pain, and nine patients who had central stenosis. In the corresponding nonresponsive local anesthetic with steroids category, the number of patients were: One who had disc herniation, six who had discogenic pain, and seven who had central stenosis. Thus, there was a high proportion of patients in the disc herniation group who were nonresponsive to lumbar interlaminar injections of local anesthetic, while there were no differences noted in the central stenosis or the discogenic pain groups compared with the corresponding responsive patients. In addition, in disc herniation, lumbar interlaminar epidural injections have somewhat superior results for pain relief at 6 months, and functional status at 12 months as observed in the local anesthetic with steroid group.[
Among the other trials, Fukusaki et al.[
Carette et al.,[
Based on multiple high-quality randomized trials[
Cervical interlaminar epidural injections
Among the trials meeting inclusion criteria, there were four high-quality trials[
All studies were conducted by Manchikanti et al.[
Based on multiple, high-quality relevant randomized trials,[
Thoracic interlaminar epidural injections
There was only one trial assessing thoracic interlaminar epidural injections. It was conducted by Manchikanti et al.,[
Manchikanti et al.,[
There was Level II evidence based on one high-quality randomized trial[
Facet joint interventions
Lumbar, cervical, and thoracic facet joint nerve blocks and cervical and lumbar intraarticular injections have been studied with saline, local anesthetic, and steroids. There were six randomized controlled trials assessing the efficacy of facet joint interventions with multiple solutions.[
Facet joint nerve blocks
Among the trials assessing facet joint nerve blocks, three of them included a 2-year follow-up, active control design, and appropriate outcome parameters.[
Based on the results of this assessment, these four trials, considered to be high-quality based on Cochrane review criteria and IPM-QRB criteria,[
Facet joint injections
There was one randomized controlled trial by Carette et al.[
Thus, there was Level I evidence for the lack of effectiveness for intraarticular injections based on two high-quality randomized controlled trials.[
Efficacy of epidural injections in specific spinal conditions
Disc herniation
Disc herniation has been treated with caudal, lumbar interlaminar, lumbar transforaminal, thoracic interlaminar, and cervical interlaminar epidural injections. There was no identifiable evidence from randomized controlled trials for either cervical transforaminal epidural injections or thoracic transforaminal epidural injections in treating disc herniation.
There were 15 trials assessing the role of epidural injections in disc herniation,[
Of the three caudal epidural injection trials, one trial[
All seven randomized controlled trials[
Of the three lumbar interlaminar epidural trials,[
There was Level I evidence, based on multiple, relevant high-quality randomized trials,[
In addition to the above, the level of evidence for each vertebral region was variable. There was Level I evidence for caudal, lumbar interlaminar, and lumbar transforaminal injections in managing lumbar disc herniation, with multiple high quality randomized controlled trials. There was also superiority for steroids in managing disc herniation in the lumbosacral region compared with local anesthetic alone in assessments up to one year with caudal and interlaminar epidural injections.
However, there was Level II evidence for managing cervical disc herniation and thoracic disc herniation based on at least one high-quality randomized controlled trial in each category.
Spinal stenosis
Caudal, lumbar interlaminar, lumbar transforaminal, thoracic interlaminar, and cervical interlaminar epidural injections have been utilized in treating pain from central spinal stenosis. There are no randomized controlled trials assessing the role of cervical or thoracic transforaminal epidural injections in managing pain of central spinal stenosis. There were seven trials assessing the role of epidural injections in central spinal stenosis,[
The caudal epidural injection trial was high quality.[
There was Level I evidence, based on relevant high-quality trials,[
There was Level II evidence in managing lumbar central spinal stenosis based on caudal and lumbar interlaminar trials, whereas there was also Level I evidence in managing cervical central spinal stenosis based on one randomized controlled trial, whereas there was no evidence available in managing thoracic spinal stenosis.
Discogenic pain
Discogenic pain has been treated with caudal, lumbar interlaminar, thoracic interlaminar, and cervical interlaminar epidural injections. There are no studies assessing the role of transforaminal epidural injections for discogenic pain.
There were three trials assessing the role of epidural injections in discogenic pain without disc herniation, radiculitis, or facet joint pain;[
There was Level I evidence, based on multiple high-quality relevant randomized controlled trials,[
There was Level II evidence based on two randomized controlled trials in managing discogenic pain with caudal and lumbar interlaminar epidural injections, with Level II evidence in managing cervical and thoracic discogenic pain, with one high-quality randomized controlled trial in each category.
Postsurgery syndrome
Postsurgery syndrome has been treated with caudal, lumbar transforaminal, thoracic interlaminar, and cervical interlaminar epidural injections. There were no studies assessing the role of lumbar interlaminar or transforaminal epidural injections.
There was only one randomized caudal epidural injection trial[
There was Level II evidence, based on the two high-quality, relevant randomized controlled trials,[
There was Level II evidence in managing lumbar postsurgery syndrome with caudal epidural injections and cervical postsurgery syndrome with cervical interlaminar epidural injections, with no evidence available for thoracic postsurgery syndrome.
DISCUSSION
In this assessment of the efficacy of various solutions injected into the spinal epidural space and over the facet joint nerves, there was Level I evidence that local anesthetics with steroids and local anesthetics or steroids administered in combination or separately were equally effective based on multiple, relevant, high-quality randomized controlled trials of spinal pain from various origins. However, for intraarticular injection, the evidence of lack of effectiveness was Level I for injections of sodium chloride solution, local anesthetic, or local anesthetic with steroids. There was also Level II evidence for the superiority of local anesthetic with steroids compared with steroids alone in managing disc herniation and Level IV evidence in spinal stenosis.
In recent years, there has been much debate in reference to interventional techniques in general, and epidural injections of steroids in particular, with catastrophic complications related to transforaminal epidural steroid injections, specifically in the cervical and thoracic spine.[
The findings of this systematic review, showing the equal effectiveness of local anesthetics alone and local anesthetics with steroid administered into the epidural space, facet joints, or over facet joint nerves, is in contrast to a long-held philosophy and belief in the medical community concerning the effectiveness of steroids in treating spinal pain based on the theory of spinal pain having an inflammatory component. The results of this study are valid as only high-quality, randomized controlled trials were utilized. Further, the grading of the evidence was based on a best-evidence synthesis utilizing a strict approach for methodological quality assessment. The long-term follow-up of one year or longer was utilized in arriving at the conclusions rather than short-term follow-up of 1, 3, 6, or even 12 weeks, etc., In fact, the results are similar to the Bicket et al.[
The findings of this systematic review may be explained by various mechanisms of steroids and local anesthetics, including the suppression of ectopic discharges from inflamed nerves, enhancing blood flow to ischemic nerve roots, the lysing of iatrogenic and inflammatory adhesions, a washout of proinflammatory cytokines, and reversal of peripheral and central sensitization.[
Noteworthy as well is that investigators may be missing the role of the nocebo effect. The implications of these results may be significant in not only designing clinical trials, but also in managing patients. Further, it is essential to understand the differences between chronic and subacute pain. Many of the studies included subacute or acute patients, leading to erroneous conclusions. In this evaluation, we also included some trials that included subacute patients; however, they were followed long-term.[
Based on this evaluation as well as the Bicket et al.[
However, these results should be interpreted in the context of their multiple limitations. Based on the results, an abundant amount of steroids is not advised. As explained, there was no meta-analysis performed. The majority of the high-quality, randomized trials included in this analysis were from one group of investigators. Consequently, further trials are essential. At present, this evidence suggests physicians carefully select patients and take the opportunity to discuss with them shared decision-making concerning the equal efficacy of local anesthetic with or without steroids in multiple conditions. Steroids with local anesthetic appear to have some superiority, even though it is derived from a low level of evidence, over local anesthetics alone in managing disc herniation.
CONCLUSION
This systematic review shows a lack of effectiveness for saline and equal effectiveness for local anesthetic alone and local anesthetic with steroids in multiple, high-quality randomized controlled trials for epidural injections for managing spinal pain in various regions for various pathologies and facet joint nerve blocks in managing facet joint pain. The results also showed the superiority of epidural steroid injections with local anesthetic over local anesthetics alone for disc herniation.
ACKNOWLEDGMENTS
The authors wish to thank Vidyasagar Pampati, MSc, for statistical assistance; Tom Prigge, MA, and Laurie Swick, BS, for manuscript review; and Tonie M. Hatton and Diane E. Neihoff, transcriptionists, for their assistance in preparation of this manuscript.
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