Safety, Efficacy of Nonparticulate and Particulate Corticosteroids in Epidural Injections

Nonparticulate corticosteroids are safer and as efficacious as particulate corticosteroids in relieving radicular pain, according to a systematic review published in Physical Medicine and Rehabilitation.¹ Based on their findings, the investigators suggest that nonparticulate corticosteroids should be the preferred treatment in patients receiving these agents via cervical and lumbosacral epidural steroid injections (ESIs) using a transforaminal approach. There was insufficient evidence for the researchers to make a recommendation on preferred steroid preparation when using a lumbar intralaminar approach.

“Given the lack of strong data favoring the efficacy of one [preparation] over the other, and the potential risk of catastrophic complications, all of which have been with particulate steroids, nonparticulate steroid preparations should be considered as first-line agents when performing ESIs,” the investigators wrote.

The systematic review included 3 cervical and 4 lumbar ESI studies, all of which were randomized trials or retrospective studies meeting a majority of the criteria in the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Successful pain control was defined as a reduction of at least 2 cm on the visual analog scale (VAS). When data were available, the researchers also examined functional outcomes and the percentage of individuals with a pain reduction of at least 50%, 70%, or 75%.

Data from cervical ESI studies examined for the review revealed more consistent results, with no statistically significant difference in pain reduction on VAS between patients receiving particulate vs nonparticulate preparations. Considering this information in the context of 13 reported cases of spinal cord ischemia following the use of particulate steroids, the use of nonparticulate steroids — such as dexamethasone — over particulate steroids — such as triamcinolone, methylprednisolone, or betamethasone — is recommended in this setting. Based on the quality of the cervical ESI studies, the investigators graded their recommendation as a B, indicating a fair level of evidence.   

The efficacy data were more divergent for lumbar transforaminal ESIs, with some studies showing higher efficacy on the VAS with particulate agents and others showing similar efficacy or improved function with nonparticulate steroids. However, the cumulative efficacy findings favoring particulate corticosteroids were not significant enough to warrant their preferred use in this setting and did not outweigh the safety concerns, which included 19 reported cases of infarction after the use of a particulate steroid during lumbar ESI. Based on these findings and the quality of evidence, the use of nonparticulate corticosteroids is advised in this setting, a recommendation also graded as a B.

A database search uncovered a single study evaluating particulate vs nonparticulate corticosteroids in patients receiving lumbar intralaminar ESI.² Results from this study indicated similar efficacy in pain control between agents. However, the researchers felt there were insufficient data to make a recommendation on steroid preparations for this application.

Several mechanisms leading to the safety risks observed in association with particulate corticosteroid injections have been suggested. The most agreed-upon mechanism is that increased particulate size results in embolization. In in vitro studies, triamcinolone particles were found to be 12 times larger than red blood cells (RBCs), whereas dexamethasone particles were approximately 10 times smaller than RBCs, resulting in less particle aggregation.³ More recently, particulate steroids administered intra-arterially were shown to  significantly affect microvascular perfusion in mice via the formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs.⁴

Summary & Clinical Applicability

Collectively, review findings suggest nonparticulate corticosteroids should be the preferred first-line agents when performing cervical or lumbar ESIs via a transforaminal approach because of their superior safety and comparable efficacy in reducing pain. The investigators urge further studies in order to more accurately assess the safety and efficacy of different corticosteroid formulations.

Limitations

Limitations of each of the studies included in this review include  retrospective design, small sample size, lack of dose equivalency between steroid groups, possible selection bias, lack of long-term follow-up data, and lack of functional outcome measures.

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References

1. Mehta P, Syrop I, Singh JR, Kirschner J. Systematic review of the efficacy of particulate versus nonparticulate corticosteroids in epidural injections [published online November 30, 2016]. PM R. doi: 10.1016/j.pmrj.2016.11.008
2. Kim D, Brown J. Efficacy and safety of lumbar epidural dexamethasone versus methylprednisolone in the treatment of lumbar radiculopathy: a comparison of soluble versus particulate steroids. Clin J Pain. 2011;27(6):518-522.
3. Derby R, Lee SH, Date ES, Lee JH, Lee CH. Size and aggregation of corticosteroids used for epidural injections. Pain Med. 2008;9(2):227-234.
4. Laemmel E, Segal N, Mirshahi M, et al. Deleterious effects of intra-arterial administration of particulate steroids on microvascular perfusion in a mouse model. Radiology. 2016;279:731-740.