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      Aggregation properties of triamcinolone acetonide injection in human serum: considerations when performing epidural steroid injections

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          Abstract

          Background

          Morbidity has been reported as a sequelae of crystalline steroid epidural steroid injections (ESIs), and particulate steroid size, aggregation, and embolization in brain and spinal cord may be the mechanism related to these neurologic effects.

          Objective

          The objective of the study was to examine the aggregation properties of triamcinolone acetonide in commonly used local anesthetics with and without human serum.

          Setting

          This study was conducted in an academic tertiary care center.

          Hypothesis

          Triamcinolone acetonide shows different aggregation characteristics in serum compared to a non-physiologic solution.

          Design

          Triamcinolone acetonide was mixed with lidocaine 1% (first group) and bupivacaine 0.5% (second group) in a 1:1 ratio and then mixed with either distilled water (control group) or serum ex vivo. A pathologist blinded to our hypothesis inspected all solutions under light microscopy with 100× and 400× magnifications. Total number of particulate steroid aggregates and the number of particles forming each aggregate (recorded as single, 1 double, 2 triple, 3 quadruple, 4 or large [>4} crystals) were counted. Particle size and aggregate size were measured (in μm). The ratios of quadruple to total aggregates, large to total, and quadruple with large to total aggregates were calculated. Steroid-serum solutions and steroid-sterile water were then compared.

          Results

          Triamcinolone aggregates showed an increased crystal and aggregate size when compared with other steroids. Within the triamcinolone subgroup, the mixture of lidocaine 1% and serum resulted in the largest crystal aggregates.

          Limitations

          Whole blood analysis may have provided a more physiologically accurate model but was not chosen due to poor microscopic analysis. Serum donor variability may also have affected particle characteristics.

          Conclusion

          Fewer large triamcinolone aggregates were noted in the presence of serum when compared to the non-serum control groups. However, when compared to previously studied particulate steroids, it had the largest aggregates when added to serum.

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          Most cited references 26

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          Adverse central nervous system sequelae after selective transforaminal block: the role of corticosteroids.

          Selective transforaminal epidural injections are frequently employed in the treatment of pain emanating from the spine. Complication rates are typically low and include paresthesia, hematoma, epidural abscess, meningitis, arachnoiditis and inadvertent subdural or subarachnoid injection. Persistent paraplegia after lumbar transforaminal block has been recently reported. Undetected intra-arterial injection has been implicated as a possible cause. We present a case of massive cerebellar infarction after uneventful selective cervical transforaminal block. Intra-arterial injection of corticosteroid is implicated with focus on particulate size of compound versus blood vessel dimension. Light microscopic data are presented to confirm the potential for embolic vascular occlusion. Case report; light microscopic data. A patient underwent selective transforaminal block on the right at the C5-C6 level. There was C5-C6 disc herniation documented by magnetic resonance imaging and C6 radiculopathy by electromyographic studies. Patient follow-up from medical office records. Needle placement at the C5-C6 foramen on the right was confirmed by biplanar fluoroscopy and injection of contrast medium. Frequent heme-negative aspirations were documented. In this patient, quadriparesis ensued shortly after injection of corticosteroid solution. The patient was admitted to the neurosurgical intensive care unit and ultimately underwent brainstem decompressive surgery when focal neurologic deficits became evident. Working diagnosis was massive cerebellar infarct. Light microscopic data are presented to illustrate particulate size in corticosteroid solutions and potential for embolic microvascular occlusion. Corticosteroid suspensions (and to a lesser extent solutions) contain large particles capable of occluding metarterioles and arterioles. We present a case of quadriparesis and brainstem herniation after selective cervical transforaminal block. We propose a potential role for corticosteroid particulate embolus during unintended intra-arterial injection as a potential mechanism.
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            Cervical transforaminal epidural steroid injections: more dangerous than we think?

            Survey/case series. To survey pain physicians about neurologic infarctions following cervical transforaminal epidural steroid injections (TF-ESIs). Cervical TF-ESIs are commonly performed in patients with cervical radiculopathy, although there are no randomized controlled studies supporting their efficacy. Eight case reports of brain and spinal cord infarction have been published. In addition, one of the investigators (M.S.W.) has reviewed 4 cases of major cerebellum/brainstem infarction following cervical TF-ESIs with methylprednisolone. To better characterize these complications, anonymous surveys were sent to all U.S. physician members of the American Pain Society. Respondents were asked about awareness of complications, year of occurrence, practice setting and specialty of the treating physician, use of fluoroscopy/contrast/local anesthetic/corticosteroid, doses administered, and CT/MRI/autopsy findings. Overall response rate was 21.4% (287 of 1340). In all, 78 complications were reported, including 16 vertebrobasilar brain infarcts, 12 cervical spinal cord infarcts, and 2 combined brain/spinal cord infarcts. Brain infarcts invariably involved the cerebellum, brainstem, or posterior cerebral artery territory. Thirteen cases resulted in a fatal outcome: 5 with brain infarcts, 1 with combined brain/spinal cord infarcts, 1 following high spinal anesthesia, 1 associated with a seizure, and 5 with unspecified etiology. All 4 cases with corticosteroid alone involved methylprednisolone, resulting in 3 cerebellar infarcts and 1 posterior cerebral territory infarct. Of these, 3 had fatal outcomes and 2 autopsies revealed no vertebral artery trauma. This study demonstrates a significant risk of serious neurologic injury after cervical TF-ESIs. A growing body of evidence supports an embolic mechanism, whereby inadvertent intra-arterial injection of particulate corticosteroid causes a distal infarct. Embolism to the distal basilar artery region can cause midbrain, pons, cerebellum, thalamus, temporal and occipital lobe infarctions. Other potential mechanisms of infarction include vertebral artery perforation causing dissection/thrombosis and needle-induced vasospasm.
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              Cervical transforaminal injection of corticosteroids into a radicular artery: a possible mechanism for spinal cord injury.

              Spinal cord injury has been recognized as a complication of cervical transforaminal injections, but the mechanism of injury is uncertain. In the course of a transforaminal injection, an observation was made after the initial injection of contrast medium. The contrast medium filled a radicular artery that passed to the spinal cord. The procedure was summarily abandoned, and the patient suffered no ill effects. This case demonstrates that despite using careful and accurate technique, it is possible for material to be injected into a radicular artery. Consequently, inadvertent injection of corticosteroids into a radicular artery may be the mechanism for spinal cord injury following transforaminal injections. This observation warns operators to always perform a test injection of contrast medium, and carefully check for arterial filling using real-time fluoroscopy with digital subtraction.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2019
                20 March 2019
                : 12
                : 1033-1039
                Affiliations
                [1 ]Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA, swahezi@ 123456montefiore.org
                [2 ]Burke Rehabilitation Hospital, Albert Einstein College of Medicine, White Plains, NY, USA
                [3 ]Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
                Author notes
                Correspondence: Sayed E Wahezi, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467-2401, USA, Tel +1 718 920 7246, Fax +1 718 920 2287, Email swahezi@ 123456montefiore.org
                Article
                jpr-12-1033
                10.2147/JPR.S181038
                6430988
                © 2019 Wahezi et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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