Injectable corticosteroid preparations: an embolic risk assessment by static and dynamic microscopic analysis

Abstract

Background and purpose: Transforaminal CS injections have been associated with severe adverse CNS events, including brain and spinal cord infarction. Our purpose was to describe the static and dynamic microscopic appearances of CS preparations, with an emphasis on their potential to cause adverse central nervous system events by embolic mechanisms during transforaminal injection.

Materials and methods: Pharmaceutical preparations of nondilute injectable CSs were used after appropriate mixing: MPA (40 mg/mL), TA (40 mg/mL), and DSP (8 mg/2 mL). For dynamic imaging, a novel methodology was devised to replicate the flow of crystals within spinal cord arterioles. In addition, CS preparations were mixed with plasma to assess for changes in crystal size, morphology, and tendency to aggregate.

Results: The CS preparations MPA and TA are composed of crystals of varying sizes. MPA crystal size range was 0.4-26 μm (mean, 6.94 μm), TA crystal size range 0.5-110 μm (mean, 17.4 μm), and DSP did not contain any significant crystals or particles. There was no change in the crystal morphology or propensity to aggregate after mixing with local anesthetic. After mixing with plasma, the crystals also were unchanged; however, there was a significant reduction in the size of aggregates. On dynamic imaging, these aggregates were proved to maintain their integrity and to act as potential embolization agents.

Conclusions: MPA and TA have a substantial risk of causing infarction by embolization if inadvertently injected intra-arterially at the time of TFESI. DSP is completely soluble and microscopically has no potential to obstruct arterioles. When performing cervical TFESI procedures, the administration of insoluble CSs should be avoided.

Fig 1.

Photograph of the apparatus within the microscope. Samples were injected through tubing (wide arrow) into the μ-Slide device (arrowhead demonstrates direction of flow through the channel within the device) and then exit into effluent tubing (thin arrow).

Fig 2.

Freeze frame from On-line Video 2 of MPA flowing through a 200-μm-depth channel after mixing with LA and plasma. This demonstrates the reduction in size of MPA aggregates after mixing with plasma. The white scale bar in the bottom right of the image represents 100 μm. The adjacent red circle represents the average size of a RBC at this magnification. There is a separate scale bar on the left side of the image that is somewhat obscured.

Fig 3.

Freeze frame from On-line Video 4 of TA flowing through a 200-μm-depth channel after mixing with LA and plasma. This demonstrates the near complete absence of crystal aggregation after mixing with plasma. The white scale bar in the bottom right of the image represents 100 μm. The adjacent red circle represents the average size of a RBC at this magnification. There is a separate scale bar on the left side of the image.

Fig 4.

Freeze frame from On-line Video 5 of DSP flowing through a 200-μm-depth channel after mixing with LA and plasma. The straight line at the top of the image is the edge of the channel. No crystals or significant particulates are identified. The white scale bar in the bottom right of the image represents 100 μm. The adjacent red circle represents the average size of a RBC at this magnification. There is a separate scale bar on the left side of the image.