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Letters to the Editor to:

Scientific Articles:
Gbolahan O. Okubadejo, Michael R. Talcott, Robert E. Schmidt, Aseem Sharma, Alpesh A. Patel, R. Brian Mackey, Anthony H. Guarino, Christopher J. Moran, and K. Daniel Riew
Perils of Intravascular Methylprednisolone Injection into the Vertebral Artery. An Animal Study
J Bone Joint Surg Am 2008; 90: 1932-1938 [Abstract] [Full text] [PDF]
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[Read Letter to the Editor] Drs. Okubadejo and Riew respond to Drs. Rathmell and Wainger
Gbolahan Okubadejo, MD, K. Daniel Riew, MD   (13 January 2009)
[Read Letter to the Editor] Clarifying mechanism of neurologic injury following intra-arterial injection of particulate steroid
James P. Rathmell, MD, Brian J. Wainger, MD, PhD   (13 January 2009)

Drs. Okubadejo and Riew respond to Drs. Rathmell and Wainger 13 January 2009
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Gbolahan Okubadejo, MD,
Department of Orthopaedic Surgery
University of Pittsburgh,
K. Daniel Riew, MD

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Re: Drs. Okubadejo and Riew respond to Drs. Rathmell and Wainger

gokubadejo{at}hotmail.com Gbolahan Okubadejo, MD, et al.

We thank Drs. Rathmell and Wainger for their comments regarding our paper, “Perils of Intravascular Methylprednisolone Injection into the Vertebral Artery” (1). This study found a 100% correlation between injection of the particulate steroid in the vertebral artery, and eventual mortality of the animal model used in this study - the pig. Nonparticulate steroids did not demonstrate such morbid outcomes.

Drs. Rathmell and Wainger raise the question of whether the findings of this study can be extrapolated to make long-term prognoses. Our animals were kept on ventilator support for only 4 - 6 hours after the insult to the brain with none of the four animals in the Methylprednisolone group able to maintain appropriate oxygenation without ventilator support. No formal neurologic exam could be performed on these obtunded animals. They were sacrificed following the 4 – 6 hour recovery period which was deemed as appropriate for postoperative recovery. In marked contrast, all animals in the nonparticulate group were able to ambulate and appeared completely normal.

As Drs. Rathmell and Wainger point out, it is certainly possible that, had we kept the animals alive for a longer period, they might have recovered. We agree that our results with pigs should not be used to prognosticate the long-term outcome of humans who suffer an immediate complication following particulate steroid injections; human beings are capable of overcoming and recovering from serious neurologic injuries, given enough time and proper rehabilitation. Nevertheless, there are several troubling case reports of catastrophic clinical outcomes following inadvertent injection of particulate steroids into the vertebral artery (2,3,4). In almost all instances, the patients sustained serious neurological deficits or ultimately expired. These reports suggest,unfortunately, that human correlates of our study do exist.

We also agree that, in theory,that it may be possible for artifacts related to tissue processing to produce histological findings similar to what we found. However, as the data in this study were so consistent and reproducible, and had correlates with MRI and clinical findings, we believe that it is reasonable to conclude that the radiographic and histologic changes that were observed are indeed representative of true pathology as opposed to being artifact.

In conclusion, we agree with Drs. Rathmell and Wainger that with our short-term animal study, we cannot judge the permanency of the neural injury following injection of particulate steroids. We believe that our study should serve as a cautionary note when utilizing particulate steroids for injections. Finally, we agree that there needs to be further study regarding the safety and effectiveness of non-particulate steroids before recommending its use.

References

1. Perils of intravascular methylprednisolone injection into the vertebral artery. An Animal Study. Okubadejo GO, Talcott MR, Schmidt RE et al. JBJS Am 2008; 90:1932-1938

2. Derby R, Lee SH, Kim BJ et al. Complications following cervical epidural injections by expert interventionalists in 2003. Pain Physicians 2004; 7:445-449.

3. McMillan MR, Crumpton C. Cortical blindness and neurologic injury complicating cervical transforaminal injection for cervical radiculopathy. Anesthesiology 2003; 99: 509 – 511.

4. Rozin L, Rozin R, Koehler SA et al. Death during transforaminal epidural steroid nerve root block (C7) due to perforation of the left vertebral artery. Am J Forensic Med Path 2003; 24:315 – 355.
Clarifying mechanism of neurologic injury following intra-arterial injection of particulate steroid 13 January 2009
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James P. Rathmell, MD,
Chief, Division of Pain Medicine
Department of Anesthesia & Critical Care, Massachusetts General Hospital, Boston, Massachusetts,
Brian J. Wainger, MD, PhD

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Re: Clarifying mechanism of neurologic injury following intra-arterial injection of particulate steroid

jprathmell{at}bics.bwh.harvard.edu James P. Rathmell, MD, et al.

To The Editor:

We commend Dr. Okubadejo and colleagues for the article “Perils of Intravascular Methylprednisolone Injection into the Vertebral Artery. An Animal Study” (1). They show a convincing association between intra- arterial injection of particulate steroid and catastrophic neurologic injury. This study should help to eliminate remaining questions about the mechanism of injury. We offer a caution about judging permanency of neural injury and issue a call for further study of the safety and effectiveness of non-particulate steroids, particularly dexamethasone.

In practice, patients are given days or longer to recover from neurological insult before concluding that the likelihood of improvement is minimal. Indeed, ventilated patients often require tracheostomy to progress to unassisted respiratory function. Caution in delivering a poor prognosis is paramount, especially in cases with inconclusive or absent imaging as is the case for two of the four animals that received particulate steroid. The dramatic changes on diffusion-weighted MR imaging studies that appear early following acute stroke are not predictive of the final size of the lesion and do not represent irreversibly infarcted tissue (2). To better understand the magnitude of the insult suffered by these animals, we would like to know more. How long were the animals given in order to wean from the ventilator? Did they show signs of spontaneous breathing? Did examination after recovery from any anesthetics document diffuse injury to the brainstem, corticospinal, sensory, and arousal systems? The pathology demonstrates dramatic degeneration, but correlation with the clinical exam is essential; albeit unlikely, artifacts related to tissue processing could have produced similar findings.

Cases of stroke and spinal cord infarction have been reported following presumed intra-arterial injection of particulate steroid; most have been associated with transforaminal injections (3). The exact mechanism of injury is unknown, but intra-arterial injection of particulate steroid acting as emboli has been postulated. The current study establishes a clear link between the intra-arterial injection of particulate steroid and devastating neurological injury. No complications have been reported with the non-particulate steroid dexamethasone, and this report provides encouraging data regarding the safety of this agent. Nonethless, we have limited clinical evidence that this agent is safe or effective (4). Practitioners are likely to move to routine use of dexamethasone for transforaminal injection. We must send a strong call for further study to document the safety and treatment benefits of non- particulate alternatives. For those who are injured following steroid injection, this study should not be used as evidence in determining long- term prognosis.

The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

References

1. Okubadejo GO, Talcott MR, Schmidt RE, Sharma A, Patel AA, Mackey RB, Guarino AH, Moran CJ, Riew KD. Perils of intravascular methylprednisolone injection into the vertebral artery. An animal study. J Bone Joint Surg Am 2008;90:1932-1938.

2. Mezzapesa DM, Petruzzellis M, Lucivero V, Prontera M, Tinelli A, Sancilio M, Carella A, Federico F. Multimodal MR examination in acute ischemic stroke. Neuroradiology 2006;48:238-46.

3. Rathmell JP, Aprill C, Bogduk N. Cervical transforaminal injection of steroids. Anesthesiology 2004;100:1595-600.

4. Dreyfuss P, Baker R, Bogduk N. Comparative effectiveness of cervical transforaminal injections with particulate and nonparticulate corticosteroid preparations for cervical radicular pain. Pain Med 2006;7:237-42.