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Systemic Effects of Steroids Following Epidural Steroid Injections

Abstract

Purpose of Review

Systemic absorption of corticosteroids occurs following epidural administration. Central steroid response, including sleeplessness, flushing, and non-positional headache, insomnia, hiccups, flushing, and increased radicular pain, represents some of the most common immediate or delayed adverse event related to epidural steroid injections (ESI).

Recent Findings

The systemic effects of corticosteroids themselves likely represent the most commonly encountered complications that result from ESI. These include hyperglycemia, hypothalamic-pituitary-adrenal axis suppression, decreased bone mineral density, and others.

Summary

This narrative review is an up-to-date summary of the literature related to adverse events following ESI which are attributable to the systemic effects of corticosteroids.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. •• El-Yahchouchi CA, Plastaras CT, Maus TP, Carr CM, McCormick ZL, Geske JR, et al. Adverse event rates associated with transforaminal and interlaminar epidural steroid injections: a multi-institutional study. Pain Med Malden Mass. 2016;17(2):239–49. https://doi.org/10.1111/pme.12896. This was a large, comprehensive recent review which noted central steroid response (sleeplessness, flushing, non-positional headache) was the most common adverse effect seen in 2.6% of 16,638 consecutive procedures (both TFESI and ILESI).

    Article  Google Scholar 

  2. • Younes M, Neffati F, Touzi M, Hassen-Zrour S, Fendri Y, Béjia I, et al. Systemic effects of epidural and intra-articular glucocorticoid injections in diabetic and non-diabetic patients. Jt Bone Spine Rev Rhum. 2007;74(5):472–6. https://doi.org/10.1016/j.jbspin.2006.10.009. This study found a slight elevation in BP that returned to normal 3 weeks post-ESI and found that both plasma cortisol levels and ACTH were below baseline 21 days after three high dose ESI.

    Article  CAS  Google Scholar 

  3. •• Friedly JL, Comstock BA, Heagerty PJ, Bauer Z, Rothman MS, Suri P, et al. Systemic effects of epidural steroid injections for spinal stenosis. Pain. 2018;159(5):876–83. https://doi.org/10.1097/j.pain.0000000000001158. This study demonstrates that HPA axis suppression is in fact due to the steroid itself and not other factors related to epidural injection. Longer-acting insoluble corticosteroid formulations such as methylprednisolone or triamcinolone have prolonged systemic absorption of corticosteroid when compared to betamethasone or dexamethasone.

    Article  CAS  PubMed  Google Scholar 

  4. Mandel S, Schilling J, Peterson E, Rao DS, Sanders W. A retrospective analysis of vertebral body fractures following epidural steroid injections. J Bone Joint Surg Am. 2013;95(11):961–4. https://doi.org/10.2106/JBJS.L.00844.

    Article  PubMed  Google Scholar 

  5. Singla A, Yang S, Werner BC, Cancienne JM, Nourbakhsh A, Shimer AL, et al. The impact of preoperative epidural injections on postoperative infection in lumbar fusion surgery. J Neurosurg Spine. 2017;26(5):645–9.

    Article  Google Scholar 

  6. • Kim S, Hwang B. Relationship between bone mineral density and the frequent administration of epidural steroid injections in postmenopausal women with low back pain. Pain Res Manag. 2014;19(1):30–4. This study showed greater than 10 ESI’s (mean of 14) with a cumulative triamcinolone dose of approximately 400 mg was associated with reduced BMD in postmenopausal women when compared to a matched group of women who did not receive ESI. It also demonstrated a dose-dependent relationship both in the magnitude of effect and duration of effect steroids have on BG following ESI.

    Article  Google Scholar 

  7. •• Habib G, Jabbour A, Salman J, Hakim G, Haddad H. The effect of epidural methylprednisolone acetate injection on the hypothalamic-pituitary-adrenal axis. J Clin Anesth. 2013;25(8):629–33. https://doi.org/10.1016/j.jclinane.2013.07.002. This study demonstrates a dose response relationship between steroid dose used in ESI and HPA suppression.

    Article  CAS  PubMed  Google Scholar 

  8. Kerezoudis P, Rinaldo L, Alvi MA, Hunt CL, Qu W, Maus TP, et al. The effect of epidural steroid injections on bone mineral density and vertebral fracture risk: a systematic review and critical appraisal of current literature. Pain Med Malden Mass. 2018;19(3):569–79. https://doi.org/10.1093/pm/pnx324.

    Article  Google Scholar 

  9. Strehl C, Bijlsma JWJ, de Wit M, Boers M, Caeyers N, Cutolo M, et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis. 2016;75(6):952–7. https://doi.org/10.1136/annrheumdis-2015-208916.

    Article  CAS  PubMed  Google Scholar 

  10. Lansang MC, Farmer T, Kennedy L. Diagnosing the unrecognized systemic absorption of intra-articular and epidural steroid injections. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. 2009;15(3):225–8. https://doi.org/10.4158/EP.15.3.225.

    Article  Google Scholar 

  11. Spaccarelli KC. Lumbar and caudal epidural corticosteroid injections. Mayo Clin Proc. 1996;71(2):169–78. https://doi.org/10.1016/S0025-6196(11)64510-2.

    Article  CAS  PubMed  Google Scholar 

  12. • Moon HJ, Choi KH, Lee SI, Lee OJ, Shin JW, Kim TW. Changes in blood glucose and cortisol levels after epidural or shoulder intra-articular glucocorticoid injections in diabetic or nondiabetic patients. Am J Phys Med Rehabil. 2014;93(5):372–8. https://doi.org/10.1097/PHM.0000000000000001. This study found HPA suppression lasting at least 7 days after a single ESI in non-diabetic patients and at least 21 days in diabetic patients.

    Article  PubMed  Google Scholar 

  13. El Abd O, Amadera J, Pimentel DC, Gomba L. Immediate and acute adverse effects following transforaminal epidural steroid injections with dexamethasone. Pain Physician. 2015;18(3):277–86.

    PubMed  Google Scholar 

  14. Plastaras C, McCormick ZL, Garvan C, Macron D, Joshi A, Chimes G, et al. Adverse events associated with fluoroscopically guided lumbosacral transforaminal epidural steroid injections. Spine J Off J North Am Spine Soc. 2015;15(10):2157–65. https://doi.org/10.1016/j.spinee.2015.05.034.

    Article  Google Scholar 

  15. Botwin KP, Baskin M, Rao S. Adverse effects of fluoroscopically guided interlaminar thoracic epidural steroid injections. Am J Phys Med Rehabil. 2006;85(1):14–23.

    Article  Google Scholar 

  16. Maillefert JF, Aho S, Huguenin MC, Chatard C, Peere T, Marquignon MF, et al. Systemic effects of epidural dexamethasone injections. Rev Rhum Engl Ed. 1995;62(6):429–32.

    CAS  PubMed  Google Scholar 

  17. Ward A, Watson J, Wood P, Dunne C, Kerr D. Glucocorticoid epidural for sciatica: metabolic and endocrine sequelae. Rheumatol Oxf Engl. 2002;41(1):68–71.

    Article  CAS  Google Scholar 

  18. Zufferey P, Bulliard C, Gremion G, Saugy M, So A. Systemic effects of epidural methylprednisolone injection on glucose tolerance in diabetic patients. BMC Res Notes. 2011;4:552.

    Article  CAS  Google Scholar 

  19. Gonzalez P, Laker SR, Sullivan W, Harwood JEF, Akuthota V. The effects of epidural betamethasone on blood glucose in patients with diabetes mellitus. PM R. 2009;1(4):340–5. https://doi.org/10.1016/j.pmrj.2008.12.007.

    Article  PubMed  Google Scholar 

  20. Even JL, Crosby CG, Song Y, McGirt MJ, Devin CJ. Effects of epidural steroid injections on blood glucose levels in patients with diabetes mellitus. Spine. 2012;37(1):E46–50. https://doi.org/10.1097/BRS.0b013e31821fd21f.

    Article  PubMed  Google Scholar 

  21. Abdul AJ, Ghai B, Bansal D, Sachdeva N, Bhansali A, Dhatt SS. Hypothalamic pituitary adrenocortical axis suppression following a single epidural injection of methylprednisolone acetate. Pain Physician. 2017;20(7):E991–1001.

    PubMed  Google Scholar 

  22. Kay J, Findling JW, Raff H. Epidural triamcinolone suppresses the pituitary-adrenal axis in human subjects. Anesth Analg. 1994;79(3):501–5.

    Article  CAS  Google Scholar 

  23. Jacobs S, Pullan PT, Potter JM, Shenfield GM. Adrenal suppression following extradural steroids. Anaesthesia. 1983;38(10):953–6.

    Article  CAS  Google Scholar 

  24. Chon JY, Moon HS. Salivary cortisol concentration changes after epidural steroid injection. Pain Physician. 2012;15(6):461–6.

    PubMed  Google Scholar 

  25. Carreon LY, Ong KL, Lau E, Kurtz SM, Glassman SD. Risk of osteoporotic fracture after steroid injections in patients with Medicare. Am J Orthop Belle Mead NJ. 2017;46(5):E293–300.

    PubMed  Google Scholar 

  26. Yi Y, Hwang B, Son H, Cheong I. Low bone mineral density, but not epidural steroid injection, is associated with fracture in postmenopausal women with low back pain. Pain Physician. 2012;15(6):441–9.

    PubMed  Google Scholar 

  27. Dubois EF, Wagemans MF, Verdouw BC, Zwinderman AH, Van Boxtel CJ, Dekhuijzen PNR, et al. Lack of relationships between cumulative methylprednisolone dose and bone mineral density in healthy men and postmenopausal women with chronic low back pain. Clin Rheumatol. 2003;22(1):12–7. https://doi.org/10.1007/s10067-002-0648-3.

    Article  CAS  PubMed  Google Scholar 

  28. Al-Shoha A, Rao DS, Schilling J, Peterson E, Mandel S. Effect of epidural steroid injection on bone mineral density and markers of bone turnover in postmenopausal women. Spine. 2012;37(25):E1567–71.

    Article  Google Scholar 

  29. Kang S-S, Hwang B-M, Son H, Cheong I-Y, Lee S-J, Chung T-Y. Changes in bone mineral density in postmenopausal women treated with epidural steroid injections for lower back pain. Pain Physician. 2012;15(3):229–36.

    PubMed  Google Scholar 

  30. Werner BC, Cancienne JM, Browne JA. The timing of total hip arthroplasty after intraarticular hip injection affects postoperative infection risk. J Arthroplast. 2016;31(4):820–3.

    Article  Google Scholar 

  31. Yao R, Zhou H, Choma TJ, Kwon BK, Street J. Surgical site infection in spine surgery: who is at risk? Glob Spine J. 2018;8(4 Suppl):5S–30S.

    Article  Google Scholar 

  32. Ozturk S, Akgun B, Erol FS, Onal SA, Kaplan M. Intraoperative results and postoperative clinical outcomes of lumbar microdiscectomy in patients who previously received a transforaminal anterior epidural steroid injection for lumbar radiculopathy. Turk Neurosurg. 2018;28(2):263–9.

    PubMed  Google Scholar 

  33. Yang S, Werner BC, Cancienne JM, Hassanzadeh H, Shimer AL, Shen FH, et al. Preoperative epidural injections are associated with increased risk of infection after single-level lumbar decompression. Spine J Off J North Am Spine Soc. 2016;16(2):191–6.

    Article  Google Scholar 

  34. Donnally CJ, Rush AJ, Rivera S, Vakharia RM, Vakharia AM, Massel DH, et al. An epidural steroid injection in the 6 months preceding a lumbar decompression without fusion predisposes patients to post-operative infections. J Spine Surg Hong Kong. 2018;4(3):529–33.

    Article  Google Scholar 

  35. Hartveldt S, Janssen SJ, Wood KB, Cha TD, Schwab JH, Bono CM, et al. Is there an association of epidural corticosteroid injection with postoperative surgical site infection after surgery for lumbar degenerative spine disease? Spine. 2016;41(19):1542–7.

    Article  Google Scholar 

  36. Seavey JG, Balazs GC, Steelman T, Helgeson M, Gwinn DE, Wagner SC. The effect of preoperative lumbar epidural corticosteroid injection on postoperative infection rate in patients undergoing single-level lumbar decompression. Spine J Off J North Am Spine Soc. 2017;17(9):1209–14.

    Article  Google Scholar 

  37. Zusman N, Munch JL, Ching A, Hart R, Yoo J. Preoperative epidural spinal injections increase the risk of surgical wound complications but do not affect overall complication risk or patient-perceived outcomes. J Neurosurg Spine. 2015;23(5):652–5.

    Article  Google Scholar 

  38. Cancienne JM, Werner BC, Puvanesarajah V, Singla A, Shen FH, Hassanzadeh H, et al. Does the timing of preoperative epidural steroid injection affect infection risk after ACDF or posterior cervical fusion? Spine J. 2016;16(10):S133–4.

    Article  Google Scholar 

  39. Tuel SM, Meythaler JM, Cross LL. Cushingʼs syndrome from epidural methylprednisolone. Pain. 1990;40(1):81–4. https://doi.org/10.1016/0304-3959(90)91054-M.

    Article  CAS  PubMed  Google Scholar 

  40. Boonen S, Van Distel G, Westhovens R, Dequeker J. Steroid myopathy induced by epidural triamcinolone injection. Br J Rheumatol. 1995;34(4):385–6.

    Article  CAS  Google Scholar 

  41. Sadarangani S, Berg ML, Mauck W, Rizza S. Iatrogenic Cushing syndrome secondary to ritonavir-epidural triamcinolone interaction: an illustrative case and review. Interdiscip Perspect Infect Dis. 2014;2014:1–7. https://doi.org/10.1155/2014/849432.

    Article  CAS  Google Scholar 

  42. Ramanathan R, Pau AK, Busse KH, Zemskova M, Nieman L, Kwan R, et al. Iatrogenic Cushing syndrome after epidural triamcinolone injections in an HIV type 1-infected patient receiving therapy with ritonavir-lopinavir. Clin Infect Dis Off Publ Infect Dis Soc Am. 2008;47(12):e97–9.

    Article  CAS  Google Scholar 

  43. Yombi JC, Maiter D, Belkhir L, Nzeusseu A, Vandercam B. Iatrogenic Cushing’s syndrome and secondary adrenal insufficiency after a single intra-articular administration of triamcinolone acetonide in HIV-infected patients treated with ritonavir. Clin Rheumatol. 2008;27(Suppl 2):S79–82.

    Article  Google Scholar 

  44. Gitkind AI, Shah B, Thomas M. Epidural corticosteroid injections as a possible cause of menorrhagia: a case report. Pain Med Malden Mass. 2010;11(5):713–5. https://doi.org/10.1111/j.1526-4637.2009.00775.x.

    Article  Google Scholar 

  45. Çok OY, Eker HE, Çok T, Akin Ş, Ariboğan A, Arslan G. Abnormal uterine bleeding: is it an under-reported side effect after epidural steroid injection for the management of low back pain? Pain Med Malden Mass. 2011;12(6):986. https://doi.org/10.1111/j.1526-4637.2011.01137.x.

    Article  Google Scholar 

  46. Suh-Burgmann E, Liu JY. Prospective case-control study of abnormal bleeding after outpatient corticosteroid injection. Gynecol Obstet Investig. 2017;82(3):276–82. https://doi.org/10.1159/000449502.

    Article  CAS  Google Scholar 

  47. Bhat AL, Chow DW, DePalma MJ, Garvan C, Chou L, Lenrow D, et al. Incidence of vocal cord dysfunction after fluoroscopically guided steroid injections in the axial skeleton. Arch Phys Med Rehabil. 2005;86(7):1330–2.

    Article  Google Scholar 

  48. Manjiani D, Said S, Kaye AD. Transient glaucoma after an epidural steroid injection: a case report. Ochsner J. 2015;15(1):79–82.

    PubMed  PubMed Central  Google Scholar 

  49. Odonkor CA, Smith B, Rivera K, Chhatre A. Persistent singultus associated with lumbar epidural steroid injections in a septuagenarian: a case report and review. Am J Phys Med Rehabil. 2017;96(1):e1–4. https://doi.org/10.1097/PHM.0000000000000526.

    Article  PubMed  Google Scholar 

  50. Dickerman RD, Overby C, Eisenberg M, Hollis P, Levine M. The steroid-responsive hiccup reflex arc: competitive binding to the corticosteroid-receptor? Neuro Endocrinol Lett. 2003;24(3–4):167–9.

    PubMed  Google Scholar 

  51. Habib G, Artul S, Hakim G. Annoying hiccups following intra-articular corticosteroid injection of betamethasone acetate/betamethasone sodium phosphate at the knee joint. Case Rep Rheumatol. 2013;2013:1–2.

    Article  Google Scholar 

  52. Ross DA, Cetas JS. Steroid psychosis: a review for neurosurgeons. J Neuro-Oncol. 2012;109(3):439–47. https://doi.org/10.1007/s11060-012-0919-z.

    Article  CAS  Google Scholar 

  53. Malladi AS, Gratton SB, Stone D, Scalapino KJ, Charles JF. Recurrent adverse psychiatric effects following intra-articular corticosteroid injection. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis. 2011;17(5):284–5. https://doi.org/10.1097/RHU.0b013e318227ab11.

    Article  Google Scholar 

  54. Stuart FA, Segal TY, Keady S. Adverse psychological effects of corticosteroids in children and adolescents. Arch Dis Child. 2005;90(5):500–6. https://doi.org/10.1136/adc.2003.041541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Benyamin RM, Vallejo R, Wang V, Kumar N, Cedeño DL, Tamrazi A. Acute epidural hematoma formation in cervical spine after interlaminar epidural steroid injection despite discontinuation of clopidogrel. Reg Anesth Pain Med. 2016;41(3):398–401.

    Article  CAS  Google Scholar 

  56. Kim SO, Park KK, Kwon YJ, Shin HC, Choi CS. Steroid-induced spinal epidural lipomatosis after suprasella tumor resection. Korean J Spine. 2013;10(2):88–90.

    Article  Google Scholar 

  57. Choi K-C, Kang B-U, Lee CD, Lee S-H. Rapid progression of spinal epidural lipomatosis. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc. 2012;21(Suppl 4):S408–12. https://doi.org/10.1007/s00586-011-1855-x.

    Article  Google Scholar 

  58. Danielson KD, Harrast MA. Focal spinal epidural lipomatosis after a single epidural steroid injection. PM R. 2011;3(6):590–3. https://doi.org/10.1016/j.pmrj.2010.11.009.

    Article  PubMed  Google Scholar 

  59. Tok CH, Kaur S, Gangi A. Symptomatic spinal epidural lipomatosis after a single local epidural steroid injection. Cardiovasc Intervent Radiol. 2011;34(Suppl 2):S250–5. https://doi.org/10.1007/s00270-010-9982-z.

    Article  PubMed  Google Scholar 

  60. Rekik S, Boussaid S, Abla HB, Cheour I, Ben Amor M, Elleuch M. Tachon Syndrome: rare side effect of articular injections of corticosteroids. a report of two cases. Drug Saf Case Rep. 2017;4(1):20. https://doi.org/10.1007/s40800-017-0062-z.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Hajjioui A, Nys A, Poiraudeau S, Revel M. An unusual complication of intra-articular injections of corticosteroids: Tachon syndrome. Two case reports. Ann Readaptation Med Phys Rev Sci Soc Francaise Reeducation Fonct Readaptation Med Phys. 2007;50(9):721–3, 718–20. https://doi.org/10.1016/j.annrmp.2007.06.001.

    Article  CAS  Google Scholar 

  62. Schneider B, Zheng P, Mattie R, Kennedy DJ. Safety of epidural steroid injections. Expert Opin Drug Saf. 2016;15(8):1031–9. https://doi.org/10.1080/14740338.2016.1184246.

    Article  CAS  PubMed  Google Scholar 

  63. Schneider B, Mattie R, Smith C. FactFinders for patient safety: Cumulative lifetime steroid exposure via epidural administration. Spine Intervention Society Patient Safety Committee

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Rosati, R., Schneider, B.J. Systemic Effects of Steroids Following Epidural Steroid Injections. Curr Phys Med Rehabil Rep 7, 397–403 (2019). https://doi.org/10.1007/s40141-019-00245-4

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Keywords

  • Epidural
  • Steroid
  • Injection
  • ESI
  • Systemic effects
  • HPA axis
  • Spine