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Percutaneous epidural neuroplasty: Cutting edge or potentially harmful pain management?
Regional Anesthesia and Pain Medicine 24(3): 198-201, 1999
Editorial Percutaneous Epidural Neuroplasty: Cutting Edge or Potentially Harmful Pain Management? The frustration of trying to provide pain relief to patients who present with chronic low back pain and/or chronic lumbar radiculopathy and who have failed traditional treatment modalities (i.e., surgery, rehabilitation, epidural steroid injections, medications, etc.) is well known. This frustration arises because pain relief following these accepted treatment modalities is inconsistent from patient to patient and because the long-term outcomes are generally uncertain at best. Therefore, when new methods for pain control are developed, we are obligated to insightfully and scientifically consider these methods. In this issue, Heavner et al. provide the results of a double-blinded, prospectively designed study which attempts to evaluate a potentially cutting-edge pain treatment technique (percutaneous epidural neuroplasty) for patients with failed back syndrome and/or chronic lumbar radiculopathy. Their hypothesis suggests that the addition of hyaluronidase and/or hypertonic saline to corticosteroid delivered directly (using a steerable catheter) into an epidural fibrotic lesion (as evidenced by the lack of spread of epidurally placed radiographic dye) would improve pain outcome. The technique of epidural neuroplasty is not n e w and is part of an ongoing effort by Racz et al. to evaluate this procedure for chronic low back and leg pain in those patients who have failed more traditional pain treatment approaches, presumably because of the pathologic impact of epidural fibrosis and its resultant effect of neural entrapment (1). After reviewing Heavner's manuscript, I noted a number of critical issues concerning their methodology, technique, and potential risks of epidural neuroplasty that suggest further study and debate before percutaneous epidural neuroplasty can be' recommended for general use. As referenced in their article, Heavner et al. refer to the article by Racz et al more complete description of percutaneous epidural neuroplasty in which they note the importance of using corticosteroid as part of the technique (1). Indeed, all of the patients in this present study received triamcinolone. If hypertonic saline and/or hyaluronidase are important primary therapeutic agents, then it would have been interesting in this study to include a hypertonic saline and a hypertonic saline/hyaluronidase group without corticosteroid. I think the inclusion of these two additional groups is important to more fully evaluate the efficacy and safety of both hypertonic saline and hyaluronidase. Rojiani et al. noted that myelin sheaths surrounding oligodendrocytes underwent vesicular disruption and disintegration after the injection of hypertonic saline following a period of hyponatremia (2). In other words, marked shifts in extracellular sodium concentration caused intramyelin edema and disintegration. Could the use of epidurally administered hypertonic saline be causing the same type of electrolyte shift at the level
Accepted for publication December 16, 1998.
198
Percutaneous Epidural Neuroplasty
•
of the nerve root myelin sheaths, resulting in myelin disruption? In a related study, Rojiani et al. noted that corticosteroid protected against the myelinolysis induced by extracellular sodium shift (3). Clearly, the use of hypertonic saline has been noted to cause rnyelopathy when injected intrathecally (4). Further, Rayan et al. noted that when warm normal saline was injected epineurially into the sciatic nerve of the rat, it produced intraneural degenerative changes and epineurial cellular proliferation (5). They recommended that epineurial saline not be used for peripheral neurolysis because it produced nerve damage. The neuronal location of the injectate may also be a critical point, because Racz et al. and Heavner et al. have pointed out that their results depend on the use of a steerable catheter that allows for the placement of the hypertonic salinehyaluronidase-corticosteroid solution within the fibrous scar formation and as close to the nerve root as possible (6). How can they be certain then that, after placement of the catheter, they are not epineurial, or worse, intrathecal, particularly in light of their recommendation that local anesthetic be injected into the area of fibrous scar before the hypertonic saline (6)? In addition, Racz et al. suggest that the corticosteroid also needs to be injected into the region of the scar. This would, on the surface, appear to be an important point, and without apparent risk to the patient. Thousands of epidural steroid injections are performed each year in the United States without apparent neurotoxicity. Indeed, Delaney et al. demonstrated, using both light and electron microscopy in cats at 30 and 120 days postepidural injection of triamcinolone diacetate, that the spinal root, the root of exit zone, and the meninges sustained minimal damage (7). Yet, Mackinnon et al. noted that certain corticosteroids (hydrocortisone and triamcinolone hexacetamide) have a peripheral neurotoxic effect causing widespread axonal and myelin degeneration when injected intrafascicularly (8). Therefore, it appears that the location of the injectate (hypertonic saline and corticosteroid) may be important both to the success and/or complication rate of this technique. Further, neurotoxicity studies need to be done in this clinical setting. In addition to the issue of where the injection occurs, total volume of the injectate may play a significant role in lysing adhesions. It is unclear from the study by Heavner et al. how much total volume was used in each patient, whether volume was standardized between groups, and how the injectates were blinded. In their complete technical description, it appears that approximately 50-55 mL of total injectate volume is generally used (1). At first glance, a high-volume technique would be a logical choice presumably to lyse and disrupt scar. However, the control of the spread of the injectate may be important to reduce the potential of complications. Salmon et al. mapped the spread of epidurally placed phenol in cancer patients using a radionuclide mixture (technetium-99m) sulfur colloid in a phenol/glycerin solution (9). Spread was recorded by continuous gamma camera. They noted that small volumes of phenol spread extensively in the epidural space (3 mL of the mixture spread a mean of 13.6 spinal segments) with wide variation between patients. Maximum spread was achieved in 15 minutes and was unrelated to patient position. Concern must be raised regarding the magnitude of spinal segment spread of hypertonic saline used by Heavner et al. if for no other reason than to reduce potential complications. Many clinical outcome studies in the pain management literature suffer from the lack of appropriate study design, experimental control groups, randomization, patient selection (i.e., patients with the same anatomic problem, age and sex groupings, duration of pain symptoms, etc.), and measurement sensitivity/specificity of pain intensity/outcome. The study by Heavner et al. suffers from similar problems. For example, 38 of the 59 patients had surgery, there appear to be multiple diagnoses causing the pain (i.e., low back vs radicular, etc.), a large disparity in duration of pain symptoms (2-30 years), some patients presumably
Fibuch
199
200
Regional Anesthesia and Pain Medicine Vol 24 No 3 May-June 1999
receiving rehabilitation after injection, and additional epidural neuroplasty therapy was given an average of 70 days following the initial therapy. I have to w o n d e r w h y additional neuroplasty was necessary if the original pain results achieved by Heavner et al. actually were caused by lysis of scar. Could their initial positive pain i m p r o v e m e n t be caused by neurolysis (myelin dysfunction) and not by adhesiolysis? At 2-3 m o n t h s (this is the time w h e n patients received additional neuroplasty), pain should r e t u r n if the initial i m p r o v e m e n t was caused by neural destruction or t e m p o r a r y myelin dysfunction. Finally, h o w did Heavner et al. control for a placebo effect? M a x i m u m visual analog scale (VAS) pain scores m a y vary from one point in time to a n o t h e r and m a y be significantly influenced by patient perception (10). Small sample sizes (typically 2 0 - 4 0 ) m a y magnify this effect (11). Lastly, the deterioration of b o t h the VAS m a x and the Short Form McGill Pain Questionnaire (SFM) at 1, 3, 6, and 12 m o n t h s are of concern. The variability noted (Fig. 2, Heavner et al.) b e t w e e n the VASma x and SFM m a y suggest a placebo effect, insensitivity of the m e a s u r e m e n t tools, or a changing clinical condition. In a similar study relying on epidurography and hypertonic saline in 34 patients, Devulder et al. could not demonstrate that i m p r o v e m e n t of epidural radiographic contrast spread correlated with better postinjection pain behavior. Pain improvem e n t occurred in only seven patients and for only 1 m o n t h . Long-term results were even worse (12). It appears that percutaneous epidural neuroplasty using hypertonic saline/ hyaluronidase might have a role in selective pain patients; however, the presently available o u t c o m e results are not conclusive e n o u g h to r e c o m m e n d the general use of this technique. There are e n o u g h u n a n s w e r e d questions relative to outcome, its therapeutic mechanism, and the risk of t r e a t m e n t to be cautious in its use. However, the concept of epidural neuroplasty is intriguing and m a y ultimately be a beneficial tool in our pain t r e a t m e n t a r m a m e n t a r i u m . To answer the questions concerning potentially cutting edge techniques like epidural n e u r o plasty, we n e e d a standardized animal model to test diagnostic and therapeutic procedures. Potentially high-risk pain m a n a g e m e n t techniques and therapeutic agents n e e d to be evaluated in this animal model first before widespread h u m a n use is encouraged. Finally, we n e e d better o u t c o m e measures of pain improvem e n t to evaluate n e w therapeutic tools and techniques. E.E. Fibuch, M.D.
Department of Anesthesiology University of Missouri at Kansas City School of Medicine Saint Luke's Hospital, Kansas City, Missouri
References 1. Racz GB, Heavner JE, Raj PP. Epidural neuroplasty. Semin Anesth 1997: 16: 303-312. 2. Rojiani AM, Cho ES, Sharer L, Prineas JW. Electrolyte-induced demyelineation in rats. Ultrastructural evolution. Acta Neuropathol (Berl) 1994: 88(4): 293-299. 3. Rojiani AM, Prineas JW, Cho ES. Protective effect of steroids in electrolyte-induced demyelineation. J Neuropathol Exp Neurol 1987: 46(4): 495-504. 4. Kim RC, Porter RW, Choi BH, Kim SW. Myelopathy after intrathecal administration of hypertonic saline. Neurosurgery 1988: 22: 942-944. 5. Rayan GM, Gannaway 3K, Pitha J, Dale GL. Peripheral nerve changes following epineurial injection of saline and blood in rat sciatic nerve. Clin Orthop 1985: 193: 299-307. 6. Racz GB, Heavner J. Letters to the editor: In response to article by Devulder et al. Clin JPain 1995: 11: 151-156.
Percutaneous Epidural Neuroplasty
•
7. Delaney TJ, Rowlingson JC, Carron H, Butler A. Epidural steroid effects on nerves and meninges. Anesth Analg 1980: 59: 6 1 0 - 6 1 4 . 8. Mackinnon SE, Hudson AR, Gentili F, Kline DG, Hunter D. Peripheral nerve injection injury with steroid agents. Plast Reconstr Surg I982: 69: 482-490. 9. Salmon JB, Finch PM, Lovegrove FT, Warwick A. Mapping the spread of epidural phenol in cancer pain patients by radionuclide admixture and epidural scintigraphy. Clin J Pain 1992: 8: I 8 - 2 2 . 10. McQuay HJ, Carroll D, Moore RA. Variation in the placebo effect in randomized controlled trials of analgesics: All is as blind as it seems. Pain 1996: 64: 331-335. 11. Moore RA, Collins SL, McQuay HJ. Variations in the placebo effect: The impact on individual trials and consequences for meta-analysis. Proceedings of the 8th World Congress on Pain, Progress in Pain Research and M a n a g e m e n t 1997: 8: 4 6 9 - 4 7 6 . 12. Devulder J, Bogaert L, Castille F, M o e r m a n A, Rolly C. Relevance of epidurography and epidural adhesiolysis in chronic failed back surgery patients. Clin J Pain 1995: l I : i47-150.
Fibuch
201
Editorial Percutaneous Epidural Neuroplasty: Cutting Edge or Potentially Harmful Pain Management? The frustration of trying to provide pain relief to patients who present with chronic low back pain and/or chronic lumbar radiculopathy and who have failed traditional treatment modalities (i.e., surgery, rehabilitation, epidural steroid injections, medications, etc.) is well known. This frustration arises because pain relief following these accepted treatment modalities is inconsistent from patient to patient and because the long-term outcomes are generally uncertain at best. Therefore, when new methods for pain control are developed, we are obligated to insightfully and scientifically consider these methods. In this issue, Heavner et al. provide the results of a double-blinded, prospectively designed study which attempts to evaluate a potentially cutting-edge pain treatment technique (percutaneous epidural neuroplasty) for patients with failed back syndrome and/or chronic lumbar radiculopathy. Their hypothesis suggests that the addition of hyaluronidase and/or hypertonic saline to corticosteroid delivered directly (using a steerable catheter) into an epidural fibrotic lesion (as evidenced by the lack of spread of epidurally placed radiographic dye) would improve pain outcome. The technique of epidural neuroplasty is not n e w and is part of an ongoing effort by Racz et al. to evaluate this procedure for chronic low back and leg pain in those patients who have failed more traditional pain treatment approaches, presumably because of the pathologic impact of epidural fibrosis and its resultant effect of neural entrapment (1). After reviewing Heavner's manuscript, I noted a number of critical issues concerning their methodology, technique, and potential risks of epidural neuroplasty that suggest further study and debate before percutaneous epidural neuroplasty can be' recommended for general use. As referenced in their article, Heavner et al. refer to the article by Racz et al more complete description of percutaneous epidural neuroplasty in which they note the importance of using corticosteroid as part of the technique (1). Indeed, all of the patients in this present study received triamcinolone. If hypertonic saline and/or hyaluronidase are important primary therapeutic agents, then it would have been interesting in this study to include a hypertonic saline and a hypertonic saline/hyaluronidase group without corticosteroid. I think the inclusion of these two additional groups is important to more fully evaluate the efficacy and safety of both hypertonic saline and hyaluronidase. Rojiani et al. noted that myelin sheaths surrounding oligodendrocytes underwent vesicular disruption and disintegration after the injection of hypertonic saline following a period of hyponatremia (2). In other words, marked shifts in extracellular sodium concentration caused intramyelin edema and disintegration. Could the use of epidurally administered hypertonic saline be causing the same type of electrolyte shift at the level
Accepted for publication December 16, 1998.
198
Percutaneous Epidural Neuroplasty
•
of the nerve root myelin sheaths, resulting in myelin disruption? In a related study, Rojiani et al. noted that corticosteroid protected against the myelinolysis induced by extracellular sodium shift (3). Clearly, the use of hypertonic saline has been noted to cause rnyelopathy when injected intrathecally (4). Further, Rayan et al. noted that when warm normal saline was injected epineurially into the sciatic nerve of the rat, it produced intraneural degenerative changes and epineurial cellular proliferation (5). They recommended that epineurial saline not be used for peripheral neurolysis because it produced nerve damage. The neuronal location of the injectate may also be a critical point, because Racz et al. and Heavner et al. have pointed out that their results depend on the use of a steerable catheter that allows for the placement of the hypertonic salinehyaluronidase-corticosteroid solution within the fibrous scar formation and as close to the nerve root as possible (6). How can they be certain then that, after placement of the catheter, they are not epineurial, or worse, intrathecal, particularly in light of their recommendation that local anesthetic be injected into the area of fibrous scar before the hypertonic saline (6)? In addition, Racz et al. suggest that the corticosteroid also needs to be injected into the region of the scar. This would, on the surface, appear to be an important point, and without apparent risk to the patient. Thousands of epidural steroid injections are performed each year in the United States without apparent neurotoxicity. Indeed, Delaney et al. demonstrated, using both light and electron microscopy in cats at 30 and 120 days postepidural injection of triamcinolone diacetate, that the spinal root, the root of exit zone, and the meninges sustained minimal damage (7). Yet, Mackinnon et al. noted that certain corticosteroids (hydrocortisone and triamcinolone hexacetamide) have a peripheral neurotoxic effect causing widespread axonal and myelin degeneration when injected intrafascicularly (8). Therefore, it appears that the location of the injectate (hypertonic saline and corticosteroid) may be important both to the success and/or complication rate of this technique. Further, neurotoxicity studies need to be done in this clinical setting. In addition to the issue of where the injection occurs, total volume of the injectate may play a significant role in lysing adhesions. It is unclear from the study by Heavner et al. how much total volume was used in each patient, whether volume was standardized between groups, and how the injectates were blinded. In their complete technical description, it appears that approximately 50-55 mL of total injectate volume is generally used (1). At first glance, a high-volume technique would be a logical choice presumably to lyse and disrupt scar. However, the control of the spread of the injectate may be important to reduce the potential of complications. Salmon et al. mapped the spread of epidurally placed phenol in cancer patients using a radionuclide mixture (technetium-99m) sulfur colloid in a phenol/glycerin solution (9). Spread was recorded by continuous gamma camera. They noted that small volumes of phenol spread extensively in the epidural space (3 mL of the mixture spread a mean of 13.6 spinal segments) with wide variation between patients. Maximum spread was achieved in 15 minutes and was unrelated to patient position. Concern must be raised regarding the magnitude of spinal segment spread of hypertonic saline used by Heavner et al. if for no other reason than to reduce potential complications. Many clinical outcome studies in the pain management literature suffer from the lack of appropriate study design, experimental control groups, randomization, patient selection (i.e., patients with the same anatomic problem, age and sex groupings, duration of pain symptoms, etc.), and measurement sensitivity/specificity of pain intensity/outcome. The study by Heavner et al. suffers from similar problems. For example, 38 of the 59 patients had surgery, there appear to be multiple diagnoses causing the pain (i.e., low back vs radicular, etc.), a large disparity in duration of pain symptoms (2-30 years), some patients presumably
Fibuch
199
200
Regional Anesthesia and Pain Medicine Vol 24 No 3 May-June 1999
receiving rehabilitation after injection, and additional epidural neuroplasty therapy was given an average of 70 days following the initial therapy. I have to w o n d e r w h y additional neuroplasty was necessary if the original pain results achieved by Heavner et al. actually were caused by lysis of scar. Could their initial positive pain i m p r o v e m e n t be caused by neurolysis (myelin dysfunction) and not by adhesiolysis? At 2-3 m o n t h s (this is the time w h e n patients received additional neuroplasty), pain should r e t u r n if the initial i m p r o v e m e n t was caused by neural destruction or t e m p o r a r y myelin dysfunction. Finally, h o w did Heavner et al. control for a placebo effect? M a x i m u m visual analog scale (VAS) pain scores m a y vary from one point in time to a n o t h e r and m a y be significantly influenced by patient perception (10). Small sample sizes (typically 2 0 - 4 0 ) m a y magnify this effect (11). Lastly, the deterioration of b o t h the VAS m a x and the Short Form McGill Pain Questionnaire (SFM) at 1, 3, 6, and 12 m o n t h s are of concern. The variability noted (Fig. 2, Heavner et al.) b e t w e e n the VASma x and SFM m a y suggest a placebo effect, insensitivity of the m e a s u r e m e n t tools, or a changing clinical condition. In a similar study relying on epidurography and hypertonic saline in 34 patients, Devulder et al. could not demonstrate that i m p r o v e m e n t of epidural radiographic contrast spread correlated with better postinjection pain behavior. Pain improvem e n t occurred in only seven patients and for only 1 m o n t h . Long-term results were even worse (12). It appears that percutaneous epidural neuroplasty using hypertonic saline/ hyaluronidase might have a role in selective pain patients; however, the presently available o u t c o m e results are not conclusive e n o u g h to r e c o m m e n d the general use of this technique. There are e n o u g h u n a n s w e r e d questions relative to outcome, its therapeutic mechanism, and the risk of t r e a t m e n t to be cautious in its use. However, the concept of epidural neuroplasty is intriguing and m a y ultimately be a beneficial tool in our pain t r e a t m e n t a r m a m e n t a r i u m . To answer the questions concerning potentially cutting edge techniques like epidural n e u r o plasty, we n e e d a standardized animal model to test diagnostic and therapeutic procedures. Potentially high-risk pain m a n a g e m e n t techniques and therapeutic agents n e e d to be evaluated in this animal model first before widespread h u m a n use is encouraged. Finally, we n e e d better o u t c o m e measures of pain improvem e n t to evaluate n e w therapeutic tools and techniques. E.E. Fibuch, M.D.
Department of Anesthesiology University of Missouri at Kansas City School of Medicine Saint Luke's Hospital, Kansas City, Missouri
References 1. Racz GB, Heavner JE, Raj PP. Epidural neuroplasty. Semin Anesth 1997: 16: 303-312. 2. Rojiani AM, Cho ES, Sharer L, Prineas JW. Electrolyte-induced demyelineation in rats. Ultrastructural evolution. Acta Neuropathol (Berl) 1994: 88(4): 293-299. 3. Rojiani AM, Prineas JW, Cho ES. Protective effect of steroids in electrolyte-induced demyelineation. J Neuropathol Exp Neurol 1987: 46(4): 495-504. 4. Kim RC, Porter RW, Choi BH, Kim SW. Myelopathy after intrathecal administration of hypertonic saline. Neurosurgery 1988: 22: 942-944. 5. Rayan GM, Gannaway 3K, Pitha J, Dale GL. Peripheral nerve changes following epineurial injection of saline and blood in rat sciatic nerve. Clin Orthop 1985: 193: 299-307. 6. Racz GB, Heavner J. Letters to the editor: In response to article by Devulder et al. Clin JPain 1995: 11: 151-156.
Percutaneous Epidural Neuroplasty
•
7. Delaney TJ, Rowlingson JC, Carron H, Butler A. Epidural steroid effects on nerves and meninges. Anesth Analg 1980: 59: 6 1 0 - 6 1 4 . 8. Mackinnon SE, Hudson AR, Gentili F, Kline DG, Hunter D. Peripheral nerve injection injury with steroid agents. Plast Reconstr Surg I982: 69: 482-490. 9. Salmon JB, Finch PM, Lovegrove FT, Warwick A. Mapping the spread of epidural phenol in cancer pain patients by radionuclide admixture and epidural scintigraphy. Clin J Pain 1992: 8: I 8 - 2 2 . 10. McQuay HJ, Carroll D, Moore RA. Variation in the placebo effect in randomized controlled trials of analgesics: All is as blind as it seems. Pain 1996: 64: 331-335. 11. Moore RA, Collins SL, McQuay HJ. Variations in the placebo effect: The impact on individual trials and consequences for meta-analysis. Proceedings of the 8th World Congress on Pain, Progress in Pain Research and M a n a g e m e n t 1997: 8: 4 6 9 - 4 7 6 . 12. Devulder J, Bogaert L, Castille F, M o e r m a n A, Rolly C. Relevance of epidurography and epidural adhesiolysis in chronic failed back surgery patients. Clin J Pain 1995: l I : i47-150.
Fibuch
201