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      Non-Particulate Steroids (Betamethasone Sodium Phosphate, Dexamethasone Sodium Phosphate, and Dexamethasone Palmitate) Combined with Local Anesthetics (Ropivacaine, Levobupivacaine, Bupivacaine, and Lidocaine): A Potentially Unsafe Mixture

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          Particulate steroids used in epidural steroid injections have been suspected as a cause of post-procedural embolic events. Some particulate steroids have been suspended only when the transforaminal approach is used for an epidural block of the spine. In contrast, non-particulate steroids are generally accepted for safety during epidural steroid injections. However, the safety of using a mixture of non-particulate steroids and local anesthetics is unknown. This study analyzed whether mixtures of commonly used non-particulate steroids and local anesthetics form crystals in solution.


          We mixed non-particulate steroids (betamethasone sodium phosphate, dexamethasone sodium phosphate, and dexamethasone palmitate) and local anesthetics (ropivacaine, levobupivacaine, bupivacaine, and lidocaine) at different ratios. We used fluorescence microscopy to observe whether crystals formed in mixed solutions; we also measured the pH of each steroid, local anesthetic, and the mixtures.


          Ropivacaine or levobupivacaine and betamethasone sodium phosphate produced large crystals (>50 µm). Ropivacaine or levobupivacaine and dexamethasone sodium phosphate produced small crystals (<10 µm). Lidocaine and all non-particulate steroids produced no identifiable crystals; dexamethasone palmitate and all local anesthetics did not form significant particulates. Betamethasone sodium phosphate and dexamethasone sodium phosphate demonstrated basic pH, while all local anesthetics demonstrated acidic pH. Mixtures showed a wide pH range.


          Non-particulate steroids can form crystals upon combination with local anesthetics. Crystal formation may be caused by alkalinization of steroids. The mixing of ropivacaine or levobupivacaine and betamethasone sodium phosphate may require caution during an epidural steroid injection. Lidocaine or bupivacaine is recommended as a local anesthetic. Dexamethasone palmitate is a candidate for a mixture, but additional studies on its safety and effectiveness are needed.

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          Most cited references 28

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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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              Safeguards to prevent neurologic complications after epidural steroid injections: consensus opinions from a multidisciplinary working group and national organizations.

              Epidural corticosteroid injections are a common treatment for radicular pain caused by intervertebral disc herniations, spinal stenosis, and other disorders. Although rare, catastrophic neurologic injuries, including stroke and spinal cord injury, have occurred with these injections.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                27 May 2021
                : 14
                : 1495-1504
                [1 ]Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital , Seongnam, Korea
                [2 ]Department of Anesthesiology and Pain Medicine, Seoul National University Hospital , Seoul, Korea
                [3 ]Department of Anesthesiology and Pain Medicine, Bundang Chuk Hospital , Seongnam, Korea
                [4 ]Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea
                Author notes
                Correspondence: Pyung-Bok Lee Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital , 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, 13620, KoreaTel +82-31- 787-7499Fax +82-31- 787-4063 Email painfree@snubh.org
                © 2021 Choi 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 5, Tables: 3, References: 29, Pages: 10
                Original Research


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