Jean-Denis Laredo
Ninety severe and sometimes fatal neurologic events occurring immediately after epidural injection of suspensions of particular glucocorticoids were reported to the FDA between 1997 and 2014, most being foraminal injections.1 Our team reported 5 cases of paraplegia complicating selective injections of particulate steroids in the lumbar spine.2
The almost immediate onset of neurologic deficit, as well as the MR findings performed in patients who experienced this complication, are suggestive of spinal cord ischemia following the interruption of arterial blood supply.3–6 The occlusion of distal intramedullary arteries by steroid particles via an unexpected intra-arterial injection has been incriminated as the mechanism leading to cord infarction.7
We used intravital microscopy of mouse cremaster muscles to investigate the in vivo effects of an intra-arterial injection of 4 different particulate steroids—namely methylprednisolone acetate, triamcinolone acetonide, prednisolone acetate, and cortivazol—and 1 corticosteroid solution—namely dexamethasone sodium phosphate—on microvascular perfusion.8 Intra-arterial administration of 20 microliters of a pure prednisolone acetate or triamcinolone acetonide suspension completely stopped blood flow in all arterioles and venules, while methylprednisolone acetate sharply decreased perfusion as well, although some blood flow was maintained in a few areas of the arteriolar and venular network. In contrast, intra-arterial administration of a cortivazol suspension or dexamethasone sodium phosphate solution did not change microvascular blood flow.8 The formation of macroaggregates of particulate steroids, which has been suggested to lead to vascular obliteration,9 was not observed in our animal experiments. Conversely, we found that an unexpected aggregation of red blood cells, occurring immediately after injection of the particulate steroids into the blood stream, was responsible for the obstruction of arterioles.8 The particulate steroids could directly interact with red blood cells without mediation by white blood cells or plasma proteins. Scanning electron microscopy showed that, with the administration of prednisolone acetate, triamcinolone acetonide, or methylprednisolone acetate, more than 28% of the red blood cells changed in shape and were deformed into spiculated cells.8 The same direct effect of the steroids on human red blood cells was also demonstrated in vitro.8
In 2014, the FDA issued a requirement that all injectable glucocorticoid product labels carry a warning concerning the serious neurologic events after epidural injection of corticosteroids.10 However, the warning did not distinguish any difference in the risks associated with the various injection approaches (eg, interlaminar, transforaminal, and caudal) or glucocorticoid formulations (solutions and suspensions). From our results, we suggest that the particulate steroids responsible for blood flow arrest in our experiments should no longer be used for foraminal injections, both at the cervical and at the lumbar level, and as a precaution, for epidural injections as well.