Background: Case reports of catastrophic neurological sequelae during ESIs have questioned
the safety of this procedure. A proposed mechanism is particulate steroid embolization resulting
in neuralischemia. Previous reports have described steroid clumping in common epidural injection
mixtures. We demonstrate that physiologic medium can also modify aggregation.
Objective: To inspect and compare aggregative properties of steroid preparations with and
without human serum.
Setting: Academic tertiary care center.
Hypothesis: Particulate steroids display different aggregation characteristics in serum compared
to non-physiologic solutions.
Design: Solutions were inspected under light microscopy: betamethasone sodium phosphate/
betamethasone acetate, methylprednisolone, and dexamethasone were each mixed in lidocaine
1%, bupivacaine 0.5%, or sterile water in a 1:1 ratio. All preparations were inspected under
light microscopy with 100x and 400x magnifications by a pathologist blinded to our expectations
and hypothesis. Five random viewing fields were selected within each slide and the number of
aggregates per field and the number of particles per aggregate was evaluated.
Results: The addition of serum had a significant effect on steroid particle aggregation and
number of particles per aggregate.
Limitations: This study was limited by sample size as only 2 sets of human serum samples were
tested with each preparation against one non-serum control. Additionally, as steroid preparations
were evaluated under light microscopy, the ex vivo setting must be considered in the interpretation
of results. Finally, mixing preparations with human serum as opposed to whole blood was necessary
to allow for improved visibility on light microscopy despite the fact that whole blood may be
necessary to more closely emulate in vivo coagulation setting.
Conclusions: Overall, the presence of serum resulted in fewer large steroid particle aggregates
when compared to non-serum control samples. Amongst particulate steroids, betamethasone with
bupivacaine 0.5% demonstrated the fewest and smallest particle aggregates, suggesting that
preparation may reduce the risk of embolic infarction. Methylprednisolone formed significantly
larger particles in bupivicaine 0.5% with serum compared to non-serum controls.
Key words: Corticosteroid, particulate aggregate, epidural injection, embolic infarction, serum
The effect of charge on the uptake and resistance to reduction of platinum(iv) complexes in human serum and whole blood models
